Torrey Pines Institute for Molecular Studies science image
Torrey Pines Institute for
Molecular Studies
3550 General Atomics Court, 2-129
San Diego, CA 92121-1122
USA
Scientists
Darcy B. Wilson
Member
Multiple Sclerosis

Experimental Medicine
Scientific Director

858.455.3803 - phone
858.455.3804 - fax

Multiple Sclerosis National Research Institute

Studies of Immune Regulation for Autoimmune Diseases

Research efforts in this laboratory extend from basic studies of the immunobiology of thymus derived (T) lymphocytes and their involvement in the immune response mechanism to clinical studies that explore means for down-regulating T cell activity in autoimmune disease and enhancing it for neoplastic disease.

A Possible Vaccine for Multiple Sclerosis

It is possible to silence selected clones of activated, disease-causing T cells by vaccination with small peptides that represent a portion of the antigen-specific receptor molecules on the surface of these T cells.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in humans. While the initial events involved in the onset of the disease remain obscure, there is much evidence suggesting that disease progression is caused by an episodic attack by T lymphocytes in the body's immune system against one or more neural proteins of the CNS. This autoimmune attack in the CNS leads to a patchy loss of the myelin sheath surrounding principal nerves, in turn causing an interruption of their normal function.

As appears to be true for EAE, the T lymphocytes responsible for MS in humans use a particular chain as part of the T cell antigen receptor (TCRV 6) that triggers these cells to become activated and pathogenic. In recent studies we have shown that a small fragment of this TCRV 6 protein chain can, when used as a vaccine in MS patients, eliminate all presumed disease causing T lymphocytes from the cerebral spinal fluid. This promising result may be the basis for a novel approach for the treatment of MS.

Key References 1-5

  1. Pinilla, C., Martin, R., Gran, B., Appel, J.R., Boggiano, C., Wilson, D.B., and Houghten, R.A. Exploring immunological specificity using synthetic peptide combinatorial libraries.  (1999) Current Opinion in Immunology 11:193-202.
  2. Sun, D., Whitaker, J.N. and Wilson, D.B. Regulatory T cells in experimental allergic encephalomyelitis. I. Frequency and specificity analysis in normal and immune rats of a T cell subset that inhibits disease. (1999) Intl. Immunol. 11:307-315.
  3. Sun, D., Whitaker, J.N. and Wilson, D.B. Regulatory T cells in experimental allergic encephalomyelitis. III. Comparison of disease resistance in Lewis and Fischer 344 rats. (1999) Eur. J. Immunol. 29:1101-1106.
  4. Wilson, D.B., Golding, A.B., Smith, R.A., Dafashy, T., Nelson, J., Smith, L.,Carlo, D.J., Brostoff, S.W., and Gold, D.P. (1997) Results of a phase I clinical trial of a T cell receptor peptide vaccine in patients with multiple sclerosis. I. Analysis of T cell receptor utilization in CSF cell populations. J. Neuroimmunology, 76:15-28.
  5. Gold, D.P., Smith R.A., Golding, A.B., Morgan, E.E., Dafashy, T., Nelson, J., Dively, J., Laxer, J.A., Richieri, S.P., Carlo, D.J., Brostoff, S.W., and Wilson, D.B. (1997) Results of a phase I clinical trial of a T cell receptor vaccine in patients with multiple sclerosis. II. Comparative analysis of TCR utilization in CSF T cell populations before and after vaccination with a TCRVb6 CDR2 peptide. J. Neuroimmunology 76: 29-38.

Experimental Medicine

Immune Regulation in Autoimmune Disease and Cancer

Research efforts in this laboratory extend from basic studies of the immunobiology of thymus derived (T) lymphocytes [1-3] and their involvement in the immune response mechanism to clinical studies that explore means for down-regulating T cell activity for treatment of autoimmune disease and enhancing it for dealing with infectious and neoplastic disease [4-6].

Basic Studies

The interaction between TCR and peptide/MHC molecules is a key factor in the regulation of immune responses. It follows from this that one means of regulating the immune response mechanism - making it more active for new modalities of treatment for cancer and infectious disease and diminishing its destructive effects in autoimmune disease - is by manipulating the nature of the peptide antigen recognized by T cells. The definition of these peptide epitopes is fundamental to an understanding of the immune mechanism, and it can also be applied to the design of diagnostics and synthetic vaccines.

To explore these issues, we take advantage of a significant collection of very large synthetic peptide combinatorial libraries to identify arrays of peptide ligands specific for T cell clones of clinical relevance in various animal models of autoimmune disease and cancer. With clones of known specificity, approximately 25% of these mimics are superagonists, having EC50 values 1-3 orders of magnitude more effective than the native ligand. An additional 25% are effective antagonists. Importantly, these mimic peptide agonists are effective immunogens capable of inducing T cell mediated immune responses to the native peptide ligand in vivo [6].

Immunotherapy for Multiple Sclerosis and Other Autoimmune Diseases

Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS) in humans. While the initial events involved in the onset of the disease remain obscure, there is much evidence suggesting that disease progression is caused by an episodic attack by T lymphocytes in the body's immune system against one or more neural proteins of the CNS [7]. It is possible to silence clones of activated, disease-causing T cells in two ways: by vaccination with small CNS peptides that have been modified to function as antagonists [6], or with peptides that represent a portion of the antigen-specific receptor molecules on the surface of these T cells [4-5]. The first approach directly down-regulates potential disease causing T cells in such a way that they are no longer pathogenic. The second is an indirect one, involving activation of a second population of regulatory T cells that target disease causing T cells leading to their inactivation.

Immunotherapy for Neoplastic Disease

Immunotherapy for neoplastic disease Combined with better detection strategies, surgical treatments for cancer have an excellent record of success for tumors that have not yet metastasized to other parts of the body. For metastatic disease, however, chemotherapeutic and radiological treatments, while leading to some prolongation of life, are not nearly as effective. It has long been goal of clinical research in immunology to harness the immune system to deal with metastasis in much the same way that it eliminates infectious organisms. But, immunological approaches for the treatment of metastatic disease have been plagued by the difficult problem of identifying tumor antigens to be used in the design of appropriate vaccines to stimulate T cell responses against tumors. This has led us to explore the strategy of using positional scanning combinatorial libraries and clinically relevant T cell clones to identify peptides that stimulate activation of these cells and induce immune responses that might be therapeutically useful for the treatment of metastatic disease [6].

Key References 1-7

  1. Pinilla, C., et al. Exploring immunological specificity using synthetic peptide combinatorial libraries. Current Opinion in Immunology 11:193-202, 1999.
  2. Wilson, D.B., et al. Acquired thymic tolerance and experimental allergic encephalomyelitis in the rat. I. Parameters and analysis of possible mechanisms. European J. Immunol. 28:2770-2779, 1998.
  3. Wilson, D.B., et al. Analysis of T cell receptor ß chains in Lewis rats with experimental allergic encephalomyelitis. II. Vß8.2+ T cells with limited CDR3 N region additions derive from the adult thymus. European J. Immunol. 28:1216-1224, 1998.
  4. Wilson, D.B., et al. Results of a phase I clinical trial of a T cell receptor peptide vaccine in patients with multiple sclerosis. I. Analysis of T cell receptor utilization in CSF cell populations. J. Neuroimmunology. 76: 15-28, 1997.
  5. Gold, D.P., et al., Results of a phase I clinical trial of a T cell receptor vaccine in patients with multiple sclerosis. II. Comparative analysis of TCR utilization in CSF T cell populations before and after vaccination with a TCRVß6 CDR2 peptide. J. Neuroimmunology. 76: 29-38, 1997.
  6. Wilson, D.B., et al. Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands. J. Immunol., in press, 1999 (Dec. 15 issue).
  7. Sun, D., et al. Regulatory T cells in experimental allergic encephalomyelitis. II. CD8+ T cells functionally antagonistic to CD4+ encephalitogenic MBP-specific T cells show persistent expression of FasL1. J. Neuroscience Res., in press, 1999.

Publications

  1. Blondelle, S.E., Moya, R., Schroder, K., and Wilson, D.B. Comparative immunogenicity of common rare HIV mutant peptides. Proceedings of the 19th APS. Understanding Biology Using Peptides, Blondelle, S. (Editor), 379-380, 2006.
  2. Kan-Mitchell, J., Bajcz, M., Schaubert, K.L., Price, D.A., Brenchley, J.M., Asher, T.E., Souek, D.C., Ng, H.L., Yang, O.O., Rinaldo, C.R. Jr., Benito, J.M., Hegde, R., Marincola, F.M., Boggiano, C., Wilson, D., Abrams, J., Blondelle, S.E., and Wilson, D.B. Degeneracy and repertoire of the human HIV-1 gag p 17(77-85) CTL response. J.Imm. 176:6690-6701, 2006.
  3. McMahan, R.H., McWilliams, J.A., Jordon, K.R., Dow, S.W., Wilson, D.B., and Slansky, J.E. Relating TCR-peptide-MHC affinity to immunogenicity for the design of tumor vaccines. J.Clin. Invest. 116:2543-2551, 2006.
  4. Mitchell, M.S., Lund, T.A., Sewell, A.K., Marincola, F.M., Paul, A.E., Schroder, K., Wilson, D.B., and Kan-Mitcehll, J. The cytotoxic T cell response to peptide analogs of the HLA-A*0201-restricted MUC1 signal sequence epitope, M1.2. Cancer Immunol. Immunother., Epub, July 28, 2006.
  5. Dai, Y.D., Jensen, K.P., Lehuen, A., Masteller, E.L., Bluestone, J.A., Wilson, D.B., Sercarz, E. A peptide of glutamic acid decarboxylase 65 can recruit and expand a diabetogenic T cell clone, BDC2.5, in the pancreas. J. Immunol. 175:3621-3627, 2005.
  6. Hill, A.F., Polvino, W.J., Wilson, D.B. The significance of glucose, insulin and potassium for immunology and oncology: a new model of immunity. J.Immune Based Ther. Vaccines 3:5, 2005. doi:10.1186/1476-8518-3-5
  7. Maynard, J., Petersson, K., Wilson, D.H., Adams, E.J., Blondelle, S.E., Boulanger, M.J., Wilson, D.B., Garcia, K.C. Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: Insights into MHC bias and antigen specificity. Immunity 22:81-92, 2005.
  8. Wilson, D.B. Immunology: Insulin auto-antigenicity in type 1 diabetes. Nature 438(7067):E5-E6, 2005.
  9. Hernandez, J., Schroder, K., Blondelle, S.E., Pons, F.G., Lone, Y.C., Simora, A., Langlade-Demoyen, P., Wilson, D.B., Zanetti, M. Antigenicity and immunogenicity of peptide analogues of a low affinity peptide of the human telomerase reverse transcriptase tumor antigen. Eur. J. Immunol. 34:2331-41, 2004.
  10. Judkowski, V., Rodriguez, E., Pinilla, C., Masteller, E., Bluestone, J.A., Sarvetnick, N., Wilson, D.B. Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes. Clin. Immunol. 113:29-37, 2004.
  11. Nino-Vasquez, J.J., Allicotti, G., Borras, E., Wilson, D.B., Valmori, D., Simon, R., Martin, R., Pinilla, C. A powerful combination: the use of positional scanning libraries and biometrical analysis to identify cross-reactive T cell epitopes. Mol. Immunol. 40:1063-1074, 2004.
  12. Wilson, D.B., Wilson, D.H., Schroder, K., Pinilla, C., Blondelle, S., Houghten, R.A., Garcia, K.C. Specificity and degeneracy of T cells. Mol. Immunol. 40:1047-1055, 2004
  13. Masteller, E.L., Warner, M.R., Ferlin, W., Judkowski, V., Wilson, D., Glaichenhaus, N., Bluestone, J.A. Peptide-MHC class II dimers as therapeutics to modulate antigen-specific T cell responses in autoimmune diabetes. J. Immunol. 171:5587-5595, 2003.
  14. Nepom, G., Quinn, A., Sercarz, E., Wilson, D.B. How important is GAD in the etiology of spontaneous disease in human and murine type 1 diabetes? J. Autoimmun. 20:193-194, 2003.
  15. Wilson, D.B. GAD-about BDC2.5: Peptides that stimulate BDC2.5 T cells and inhibit IDDM. J. Autoimmun. 20:199-201, 2003.
  16. You, S., Chen, C. , Lee, W.H., Wu, C.H., Judkowski, V., Pinilla, C., Wilson, D.B., Liu, C.P. Detection and characterization of T cells specific for BDC2.5 T cell-stimulating peptides. J. Immunol. 170:4011-4020, 2003.
  17. Borras, E., Martin, R., Judkowski, V., Shukaliak, J., Zhao, Y., Rubio-Godoy, V., Valmori, D., Wilson, D., Simon, R., Houghten, R., Pinilla, C. Findings on T cell specificity revealed by synthetic combinatorial libraries. J. Immunol. Methods 267:79-97, 2002.
  18. Judkowski, V., Pinilla, C., Schroder, K., Tucker, L., Sarvetnick, N., Wilson, D.B.  Identification of MHC class II-restricted peptide ligands, including a glutamic acid decarboxylase 65 sequence, that stimulate diabetogenic T cells from transgenic BDC2.5 nonobese diabetic mice. J. Immunol. 166:908-917, 2001.
  19. Houghten, R.A., Wilson, D.B., Pinilla, C. Drug and vaccine discovery using mixture-based synthetic combinatorial libraries. Drug Discovery Today 5:276-285, 2000.
  20. Pinilla, C., Appel, J.R., Blondelle, S.E., Dooley, C.T., Eichler, J., Nefzi, A., Ostresh, J.M., Martin, R., Wilson, D.B., Houghten, R.A. Synthesis and screening of positional scanning synthetic combinatorial libraries. In: Combinatorial Chemistry: A Practical Approach (Fenniri, H., Ed.), Oxford University Press, Oxford, pp. 51-74, 2000.
  21. Pinilla, C., Houghten, R.A., Wilson, D.B., Martin, R. Identification and optimization of antigens for T cell clones of clinical relevance using positional scanning combinatorial libraries. In: Peptides for the New Millenium, Proceedings of the 16th American Peptide Symposium (Fields, G.B., Tam, J.P., Barany, G., Eds.), Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 683-684, 2000.
  22. Pinilla, C., Martin, R., Gran, B., Appel, J.R., Boggiano, C., Wilson, D.B., Houghten, R.A. Exploring immunological specificity using synthetic peptide combinatorial libraries. Current Opinion in Immunology 11:193-202, 1999.
  23. Sun, D., Whitaker, J.N., Wilson, D.B. Regulatory T cells in experimental allergic encephalomyelitis. I. Frequency and specificity analysis in normal and immune rats of a T cell subset that inhibits disease. Int. Immunol. 11:307-315, 1999.
  24. Sun, D., Whitaker, J.N., Wilson, D.B. Regulatory T cells in experimental allergic encephalomyelitis. III. Comparison of disease resistance in Lewis and Fischer 344 rats. Eur. J. Immunol. 29:1101-1106, 1999.
  25. Wilson, D., Pinilla, C., Wilson, D.H., Schroder, K, Boggiano, C., Judkowski, V., Kaye, J., Hemmer, B., Martin, R., Houghten, R. Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands. J. Immunol.  163:6424-6434, 1999.
  26. Sun, D., Wilson, D.B., Cao, L., Whitaker, J.N. The role of regulatory T cells in Lewis rats resistant to EAE. J. Neuroimmunology. 81:177-183, 1998.
  27. Wilson, D.B., Schroder, K., Mueller, D., Golding, A.B., Wilson, D.H., Gold, D.P. Analysis of T cell receptor ß chains in Lewis rats with experimental allergic encephalomyelitis. II. Vß8.2+ T cells with limited CDR3 N region additions derive from the adult thymus. Eur. J. Immunol. 28:1216-1224, 1998.
  28. Wilson, D.B., Schroder, K., Wilson, D.H. Acquired thymic tolerance and experimental allergic encephalomyelitis in the rat. I. Parameters and analysis of possible mechanisms. Eur. J. Immunol. 28:2770-2779, 1998.
  29. Gold, D.P., Schroder, K., Golding, A., Brostoff, S.W., Wilson, D.B. T cell receptor peptides as immunotherapy for autoimmune disease. Critical Reviews in Immunology 17:507-510, 1997.
  30. Gold, D.P., Smith R.A., Golding, A.B., Morgan, E.E., Dafashy, T., Nelson, J., Dively, J., Laxer, J.A., Richieri, S.P., Carlo, D.J., Brostoff, S.W., Wilson, D.B. Results of a phase I clinical trial of a T cell receptor vaccine in patients with multiple sclerosis. II. Comparative analysis of TCR utilization in CSF T cell populations before and after vaccination with a TCRVβ6 CDR2 peptide. J. Neuroimmunology. 76:29-38, 1997.
  31. Wilson, D.B., Golding, A.B., Smith, R.A., Dafashy, T., Nelson, J., Smith, L., Carlo, D.J., Brostoff, S.W., Gold, D.P. Results of a phase I clinical trial of a T cell receptor peptide vaccine in patients with multiple sclerosis. I. Analysis of T cell receptor utilization in CSF cell populations. J. Neuroimmunology. 76:15-28, 1997.
  32. Gold, D.P., Schroder, K., Mueller, D., Wilson, D.B. Analysis of T cell receptor β chains in the rat. I. Allelic polymorphism of Vβ8.2 is not a predisposing genetic factor in susceptibility to experimental allergic encephalomyelitis. J. Neuroscience Research. 45:700-705, 1996.
  33. Sobol, R.E., Royston, I., Fakhrai, H., Shawler, D.L., Carson, C., Dorigo, O., Gjerset, R., Gold, D.P., Koziol, J., Mercola, D., Van Beveren, C., Wilson, D.B. Injection of colon carcinoma patients with autologous irradiated tumor cells and fibroblasts genetically modified to secrete interleukin-2 (IL-2): A phase I study. Human Gene Therapy. 6:195-204, 1995. 
  34. Gold, D.P, Surh, C.D., Sellins, K.S., Schroder, K., Sprent, J., Wilson, D.B. Rat T cell responses to superantigens. II. Allelic differences in Vá8.2 and Vá 8.5á chains determine responsiveness to staphylococcal enterotoxin B and mouse mammary tumor virus encoded products. J. Exp. Med. 179:63-69, 1994. 
  35. Wilson, D.B., Steinman, L., Gold, D.P. The V-region disease hypothesis: new evidence suggests it is probably wrong. Immunol. Today 14:376-380, 1993. 130. Surh, C.D., Gold, D.P., Wilson, D.B., Sprent, J. Rat T cell responses to superantigens. I. Vá-restricted clonal deletion of rat T cells diff J. Exp. Med. 179:57-62, 1994.
  36. Davies, J.D., Silvers, W.K., Wilson, D.B. A transplantation antigen, possibly of mitochondrial origin, that elicits rejection of parental strain skin grafts by F1 rats. Transplantation 54:730-731, 1992. 
  37. Davies, J.D., Wilson, D.H., Butcher, G.A., Wilson, D.B. Generation of T cells with lytic specificity for atypical antigens. II. A novel antigen system in the rat dependent on homozygous expression of major histocompatibility complex genes of the class I-like RT1C region. J. Exp. Med. 173:833, 1991.
  38. Davies, J.D., Wilson, D.H., Hermel, E., Fischer Lindahl, K., Butcher, G.A., Wilson, D.B. Generation of T cells with lytic specificity for atypical antigens. I. A mitochondrial antigen in the rat. J. Exp. Med. 173:823, 1991.
  39. Davies, J.D., Wilson, D.H., Wilson, D.B. Generation of T cells with lytic specificity for atypical antigens. III. Priming F1 animals with antigen-bearing cells also having reactivity for host alloantigens allows for potent lytic T cell responses. J. Exp. Med. 173:841, 1991.
  40. Gold, D.P., Offner, H., Sun, D., Wiley, S., Vandenbark, A.A., Wilson, D.B. Analysis of T cell receptor á chains in Lewis rats with experimental allergic encephalomyelitis. Conserved CDR3 regions. J. Exp. Med. 174:1467-1476, 1991. 
  41. Mosier, D.E., Gulizia, R.J., Baird, S.M., Wilson, D.B., Spector, D.H., Spector, S.A. Human immunodeficiency virus infection of human-PBL-SCID mice. Science 251:791-794, 1991.
  42. Babcock, S.K., Niswender, K., Wilson, D.B., Bellgrau, D. Cyclosporine induced autoimmunity in rats carrying thymus allografts. Transplantation. 50:278, 1990.
  43. Davies, J.D., Mueller, D., Wilson, D.B., Gold, D.P. Nucleotide sequence of a cDNA encoding the rat T3 delta chain. Nucleic Acids Res. 18:4617, 1990.
  44. Davies, J.D., Wilson, D.H., Hermel, E., Fischer Lindahl, K., Butcher, G.A., Wilson, D.B. A maternally-transmitted antigen system in the rat. Transplantation Proc. 22:2547-2548, 1990. 
  45. Mosier, D.E., Baird, S.M., Kirven, M.B., Gulizia, R.J., Wilson, D.B., Kobayashi, R., Picchio, G., Garnier, J.L., Sullivan, J.L., Kipps, T. EBV-associated B cell lymphomas following transfer of human peripheral blood lymphocytes to mice with severe combined immune deficiency. In: Current Topics in Microbiology and Immunology, M. Potter and F.J. Melchers, eds. (Springer-Verlag, Berlin-Heidelberg, 1990, pp. 317-324.
  46. Wilson, D.B., Feldmann, M. Autoimmunity and immunogenicity of self tissues. In: Immunogenicity, UCLA Symp. Molec. Cell. Biol., New Series, Vol. 113. C. Janeway, J. Sprent, E. Sercarz, eds. Alan R. Liss, Inc., New York. 1990.
  47. Mosier, D.E., Gulizia, R.J., Baird, S.M., Richman, D.D., Wilson, D.B., Fox, R.I., Kipps, T.J. B cell lymphomas in SCID mice engrafted with human peripheral blood leukocytes. Blood 74 (Suppl. 1):52a, 1989. 
  48. Mosier, D.E., Gulizia, R.J., Baird, S.M., Spector, S., Spector, D., Kipps, T.J., Fox, R.I., Carson, D.A., Cooper, N., Richman, D.D., Wilson, D.B. Studies of HIV infection and the development of Epstein-Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency. In: Current Topics in Microbiology and Immunology, M.J. Bosma, R.A. Phillips and W. Schuler, eds. (Springer Verlag, Heidelberg, 1989) 152, pp. 195-199.
  49. Mosier, D.E., Gulizia, R.J., Baird, S.M., Wilson, D.B. On the SCIDs? Nature 338:211, 1989.
  50. Mosier, D.E., Gulizia, R.J., Wilson, D.B., Baird, S.M., Spector, S.A., Spector, D.H., Richman, D.D., Fox, R.I., Kipps, T.J. Elements of the human immune system: Studies of mature lymphoid cells following xenotransplantation to SCID mice. In: Progress in Immunology VII. F. Melchers, et al., eds. Springer-Verlag, Berlin, 1989. pp. 1264-1271.
  51. Wilson, D.B. Idiotypic regulation of T cells in graft-versus-host disease and autoimmunity. Immunol. Rev. 107:159, 1989.
  52. Mosier, D.E., Gulizia, R.J., Baird, S.M., Wilson, D.B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256-259, 1988. 
  53. Falk, J., Festenstein, H., Moller, E., Wilson, D.B. Immunogenetics and histocompatibility. Transpl. Proc. Vol. XIX, No. 1:902, 1987. 
  54. Hart, M.K., Kornbluth, J., Main, E.K., Spear, B.T., Taylor, J., Wilson, D.B. Lymphocyte function-associated antigen one (LFA-1) and natural killer (NK) cell activity: LFA-1 is not necessary for all killer:target cell interactions. Cellular Immunol. 109:306, 1987.
  55. Kimura, H., Silvers, W.K., Wilson, D.B. Immunogenicity and cross-reactivity of specificity associated markers on alloreactive T cells: Confirmation based on the model of tolerance abolition by adoptive transfer. J. Exp. Med. 163:469, 1986.
  56. Sorokin, R., Kimura, H., Schroder, K., Wilson, D.H., Wilson, D.B. Cyclosporine induced autoimmunity: Conditions for expressing the disease, the requirement for an intact thymus and potency estimates of autoimmune lymphocytes in drug-treated rats. J. Exp. Med. 164:1615, 1986. 
  57. Spear, B.T., Kornbluth, J., Strominger, J.L., Wilson, D.B. Evidence for a shared HLA-A intralocus determinant defined by monoclonal antibody 131. J. Exp. Med. 162:1802, 1986.
  58. Kornbluth, J., Spear, B., Raab, S.S., Wilson, D.B. Evidence for the role of class I and class II HLA antigens in the lytic function of a cloned line of human natural killer cells. J. Immunol. 134:728-735, 1985.
  59. Main, E.K., Lampson, L.A., Hart, M.K., Kornbluth, J., Wilson, D.B. Human neuroblastoma cell lines are susceptible to lysis by natural killer cells but not by cytotoxic T lymphocytes. J. Immunol. 135:242-246, 1985.
  60. Spear, B., Kornbluth, J., Strominger, J.L., Wilson, D.B. Characterization of an HLA-A locus specific monoclonal antibody. In: Advances in Gene Technology: Molecular Biology of the Immune System, J.W. Streilein, et al eds, Cambridge University Press, Cambridge, U.K., p. 313, 1985. 
  61. Webb, S.R., Hu-Li, J., MacNeil, I., Marrack, P., Sprent, J., Wilson, D.B. T cell receptors for responses to Mls determinants and allo-H-2 determinants appear to be encoded on different chromosomes. J. Exp. Med. 161:269, 1985.
  62. Webb, S.R., Ju-Li, J., Wilson, D.B., Sprent, J. Capacity of small B cell-enriched populations to stimulate mixed lymphocyte reactions: Marked differences between irradiated versus mitomycin C-treated stimulators. Eur. J. Immunol. 15:92, 1985.
  63. Kimura, H., Pickard, A., Wilson, D.B. Analysis of T cell populations that induce and mediate specific resistance to graft-versus-host disease in rats. J. Exp. Med. 160:652, 1984.
  64. Kimura, H., Wilson, D.B. Anti-idiotypic cytotoxic T cells in rats with graft-versus-host disease. Nature 308:463, 1984.
  65. Kornbluth, J., Raab, S.S., Wilson, D.B. Inhibition of cell-mediated lympholysis by cloned and uncloned lines of natural killer (NK) cells and cytotoxic T-lymphocytes (CTL) with sugars and lectins. Cellular Immunol. 88:162, 1984.
  66. Kornbluth, J., Wilson, D.B. Monoclonal antibodies directed against HLA molecules affect the lytic and proliferative behavior of a cloned line of human natural killer cells. Human Immunol. 11:239, 1984.
  67. Main, E.K., Hart, M.K., Wilson, D.B. Immunofiltration --a rapid screening assay for detection of antibodies directed against cell surface antigens. In: Monoclonal Antibodies and Functional Cell Lines, R. Kennett, K. Bechtol and T. McKearn, eds., Plenum Press, p. 376, 1984. 
  68. Webb, S.R., Mosier, D.E., Wilson, D.B., Sprent, J. Negative selection in vivo reveals expression of strong Mls determinants in mice with X-linked immunodeficiency. J. Exp. Med. 160:108, 1984.
  69. Wilson, D.B. Idiotypic regulation of self-reactive and allo-reactive T cells in autoimmunity and graft-versus-host disease. Immunol. Today 5:228, 1984.
  70. Hickey, W.F., Gonatas, N.K., Kimura, H., Wilson, D.B. Identification and quantitation of T lymphocyte subsets found in the spinal cord of the Lewis rat during acute experimental allergic encephalomyelitis. J. Immunol. 131:2805-2809, 1983. 
  71. Potter, T.A., Pallidino, M.D., Wilson, D.B., Rajan, T.V. Epitopes on H-2Dd somatic cell mutants recognized by cytotoxic T lymphocytes. J. Exp. Med. 158:1061, 1983.
  72. Webb, S., Bruce, J., Molnar-Kimber, K., Wilson, D.B., Sprent, J. Anti-H-2 reactivity of Mls specific T-cell clones. In: Isolation, Characterization and Utilization of T Lymphocyte Clones. F. W. Fitch and C.G. Fathman, eds. pp. 332-339, 1982. 
  73. Wilson, D.B., Bellgrau, D.L. Speculations on the nature of allospecific T-cell receptors and the mechanism of tolerance for self-MHC gene products. Behring Inst. Mitt. 70:210, 1982.
  74. Bellgrau, D., Smilek, D., Wilson, D.B. Induced tolerance in F1 rats to anti-major histocompatibility complex receptors on parental T cells. Implications for self tolerance. J. Exp. Med. 153:1660, 1981.
  75. Massey, G.R., Wilson, D.B. Presentation to T cells of antigens under Ir control in the rat. Transpl. Proc. 13:1397, 1981.
  76. Sieck, T., Wilson, D.B. Studies of the MHC-linked "CT" alloantigenic system in rats. II. Evidence for more than one locus and several different determinants. Immunogenetics 14:293, 1981.
  77. Snodgrass, H.R., Bosma, M.J., Wilson, D.B. T lymphocytes specific for immunoglobulin allotype. II. Cloned Igh-1b specific cytotoxic T cells. J. Exp. Med. 154:491, 1981.
  78. Snodgrass, H.R., Wilson, D.B., Bosma, M.J. T lymphocytes specific for immunoglobulin allotype. I. Igh-1b specific T cells demonstrated by suppression in vivo and cytotoxicity in vitro. J. Exp. Med. 154:480, 1981.
  79. Webb, S.R., Molnar-Kimber, K., Bruce, J., Sprent, J., Wilson, D.B. T cell clones with dual specificity for Mls and various MHC determinants. J. Exp. Med. 154:1970, 1981. 
  80. Molnar-Kimber, K.L., Webb, S.R., Sprent, J., Wilson, D.B. T-cell lines with dual specificity for strong Mls and H-2 determinants. J. Immunol. 125:2643-2645, 1980. 
  81. Smilek, D.E., Boyd, H.C., Wilson, D.B., Zmijewski, C.M., Fitch, F.W., McKearn, T.J. Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, human target cells. J. Exp. Med. 151:1139, 1980.
  82. Wilson, D.B., Smilek, D., Bellgrau, D.L. T cell mediated immune response to anti-MHC receptors. In: Regulatory T Lymphocytes. Pernis and Vogel, eds. Academic Press, Inc., New York, pp. 75-87, 1980.
  83. Bellgrau, D.L., Wilson, D.B. Immunological studies of T cell receptors. II. Limited polymorphism of idiotypic determinants on receptors specific for MHC alloantigens. J. Exp. Med. 149:234, 1979.
  84. Marchalonis, J.J., Wilson, D.B., Givol, D. Molecular and cellular characterization of antigen-binding receptor. In: T and B Lymphocytes: Recognition and Function, F.H. Bach, B. Bonavida, E.S. Vitetta and C.F. Fox, eds. Vol. XVI, pp. 481-484, 1979. 
  85. Sieck, T., Marshak-Rothstein, A., Wilson, D.B. Studies of the MHC-linked "CT" alloantigenic system in rats. I. Neither an SD or an LD gene product. Immunogenetics 9:165, 1979.
  86. Snodgrass, H.R., Bosma, M., Wilson, D.B. Immune lymphocytes of transferring allotype suppression contain cytotoxic T cells specific for allotypic determinants. J. Supramolec. Struct. Suppl. 3:771, 1979.
  87. Bellgrau, D.L., Wilson, D.B. Immunological studies of T cell receptors. I. Specifically induced resistance to graft-versus-host disease in rats mediated by host T cell immunity to alloreactive parental T cells. J. Exp. Med. 148:103, 1978. 
  88. Sieck, T., Marshak, A., Wilson, D.B. CT: A new class of MHC-linked determinants in the rat. Fed. Proc. 37:1161, 1978 (abstract).
  89. Bellgrau, D.L., Wilson, D.B. Specifically induced resistance to systemic GVH disease in rats. In: Regulation of the Immune System, E. Sercarz and L. Herzenberg, eds. p. 159, 1977.
  90. Bellgrau, D.L., Wilson, D.B. Specificity of induced GVH resistance in rats. J. Supramolec. Struct. Suppl. 1:230, 1977.
  91. Lindahl, K.F., Wilson, D.B. Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro. J. Exp. Med. 145:500, 1977.
  92. Lindahl, K.F., Wilson, D.B. Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. J. Exp. Med. 145:508, 1977.
  93. Marshak, A., Doherty, P.C., Wilson, D.B. The control of specificity of cytotoxic T lymphocytes by the major histocompatibility complex (Ag-B) in rats and identification of a new alloantigen system showing no Ag-B restriction. J. Exp. Med. 146:1773, 1977. 
  94. Marshak, A., Wilson, D.B. Recognition of minor antigenic determinants by rat cytotoxic T cells. J. Supramolec. Struct. Suppl. 1:177, 1977.
  95. Wigzell, H., Katz, M., Wilson, D.B. Multiplicity of T cell receptors. In: Regulation of the Immune System, E. Sercarz and L. Herzenberg, eds. p. 159, 1977.
  96. Wilson, D.B., Heber-Katz, E., Marshak, A., Lindahl, K.F. Considerations of the nature and specificity of T cell triggering and of cell-cell interactions in the immune responses. In: Development of Host Defenses, M.D. Cooper and D.H. Dayton, eds. Raven Press, pp. 133-140, 1977.
  97. Wilson, D.B., Heber-Katz, E., Sprent, J., Howard, J.C. On the possibility of multiple receptor specificities on T cells. Cold Spring Harbor Symp. Quant. Biol. 41:559, 1977.
  98. Wilson, D.B., Lindahl, K.F., Wilson, D.H., Sprent, J. The generation of killer cells to TNP-modified allogeneic targets by lymphocyte populations negatively selected to strong alloantigens. J. Exp. Med. 146:361, 1977.
  99. Woodland, R.T., Wilson, D.B. The induction of specific resistance in F1 hybrid rats to local graft-versus-host reactions: Nature of the eliciting cell. Eur. J. Immunol. 7:136, 1977.
  100. Bellgrau, D.L., Woodland, R.T., Wilson, D.B. Specific graft-versus-host (GVH) resistance induced in F1 rats with parental lymphocytes and demonstrable by alteration of recirculation dynamics of parental lymphocytes. Fed. Proc. 35:473, 1976 (abstract).
  101. Fox, D.H., Rowlands, Jr., D.T., Wilson, D.B. Proliferative reactivity of opposum peripheral blood leucocytes to allogeneic cells, mitogens, specific antigens. Transpl. 21:164, 1976.
  102. Heber-Katz, E., Wilson, D.B. Sheep red blood cell specific helper activity in rat TDL populations positively selected for MLR and GVH reactivity to specific strong histocompatibility alloantigens. J. Exp. Med. 143:701, 1976.
  103. Wilson, D.B., Heber-Katz, E., Woodland, R.T., Howard, J.C. Responses of alloantigen reactive lymphocytes to conventional antigens. In: Brooklodge Conference on The Role of the Products of the Major Histocompatibility Gene Complex in Immune Responses, D.H. Katz and B. Benacerraf, eds. Academic Press, Inc., New York, pp. 179-182, 1976.
  104. Wilson, D.B., Marshak, A., Howard, J.C. Specific positive and negative selection of rat lymphocytes reactive to strong histocompatibility antigens. Activation with alloantigens in vitro and in vivo. J. Immunol. 116:1030, 1976.
  105. Wilson, D.B., Marshak, A., Pierson, G., Howard, J.C. Specific selection of cytotoxic effector cells. The generation of cytotoxic T cells in rat thoracic duct lymphocyte populations positively or negatively selected for reactivity to specific histocompatibility alloantigens. J. Immunol. 116:1624, 1976.
  106. Heber-Katz, E., Wilson, D.B. Collaboration of allogeneic T and B lymphocytes in the primary antibody response to sheep erythrocytes in vitro. J. Exp. Med. 142:928, 1975.
  107. Heber-Katz, E., Wilson, D.B. Collaboration of allogeneic T and B lymphocytes in the primary antibody response to sheep erythrocytes in vitro. In: Mitogens in Immunobiology. J.J. Oppenheim and D.L. Rosenstreich, eds. Academic Press, Inc., New York, pp. 375-383, 1975. 
  108. Nowell, P.C., Finan, J.B., Wilson, D.B. Proliferation in vivo of T lymphocytes reactive to strong histocompatibility alloantigens: A correction. J. Exp. Med. 142:230, 1975.
  109. Howard, J.C., Wilson, D.B. Specific positive selection of lymphocytes reactive to strong histocompatibility antigens. J. Exp. Med. 140:660, 1974.
  110. Wilson, D.B. Immunologic reactivity to major histocompatibility alloantigens. HARC, effector cells and the problem of memory. Proc. II Int. Congr. Immunol. Progr. Immunol., pp. 145-156, 1974. 
  111. Elkins, W.L., Adams, J.S., Fox, D.H., Wilson, D.B., Stuart, F.P. Partial tolerance and immunity after adoptive abrogation of transplantation tolerance in the rat. Cell. Immunol. 9:412, 1973.
  112. Palm, J.E., Wilson, D.B. The Ag-B locus of rats: A major histocompatibility complex. Transpl. Proc. 5:1573, 1973. 
  113. Wilson, D.B., Howard, J.C. Specific positive selection for rat lymphocytes (HARC) reactive to strong transplantation antigens. Fed. Proc. 32:1006, 1973 (abstract).
  114. Wilson, D.B., Howard, J.C., Nowell, P.C. Some biological aspects of lymphocytes reactive to strong histocompatibility alloantigens (review). Transpl. Rev. 12:3, 1973.
  115. Wilson, D.B., Nowell, P.C. Heterogeneity of T lymphocytes reactive to histocompatibility alloantigens with respect to life span and distribution in blood and lymph. Proc. 7th Leukocyte Culture Conf., Point-au-Pic, Quebec, Canada. p. 245, 1973. 
  116. Maurer, P.H., Wilson, D.B., Merryman, C. Genetic control of immune response in inbred mice. Fed. Proc. 31:3161, 1972 (abstract).
  117. Wilson, D.B. Antigens, lymphoid cells, the immune response. (Review of book by G.J.V. Nossal). Science, 1972. 
  118. Wilson, D.B., Nowell, P.C. Differences in the life history of lymphocytes reactive to histocompatibility antigens. Fed. Proc. 31:609, 1972 (abstract).
  119. Nowell, P.C., Wilson, D.B. Lymphocytes and hemic stem cells. Am. J. Pathol. 65:641, 1971.
  120. Nowell, P.C., Wilson, D.B. Studies on the life history of lymphocytes. I. The life span of cells responsive in the mixed lymphocyte interaction. J. Exp. Med. 134:1131, 1971.
  121. Wilson, D.B. The mixed lymphocyte interaction: Disquisitions on a popular unknown. Progr. Immunol. I, Proc. First Internatl. Congress Immunol., Academic Press. pp. 1045-1058, 1971.
  122. Wilson, D.B., Fox, D.H. Quantitative studies on the mixed lymphocyte interaction in rats. VI. Reactivity of cells from conventional and pathogen-free rats to homologous and heterologous histocompatibility antigens. J. Exp. Med. 134:857, 1971.
  123. Wilson, D.B., Nowell, P.C. Primary and "secondary" immunologic reactivity of lymphocytes to histocompatibility antigens: A consideration of immunologic memory. In: Proceedings of the Third Sigrid Juselius Symposium of Cell Interactions and Receptor Antibodies in Immune Responses. Academic Press, Helsinki. pp. 277-299, 1971. 
  124. Wilson, D.B., Nowell, P.C. Quantitative studies on the mixed lymphocyte interaction in rats. V. Tempo and specificity of the proliferative response and the number of reactive cells from immunized donors. J. Exp. Med. 133:442, 1971.
  125. Wilson, D.B., Nowell, P.C. The cellular basis of immunologic memory to major histocompatibility antigens. Fed. Proc. 30:357, 1971 (abstract).
  126. Wilson, D.B., Weissman, G. Lymphocyte activation. Progr. Immunol. 1:1143, 1971.
  127. Johnston, J.M., Wilson, D.B. Origin of immunoreactive lymphocytes in rats. Cell. Immunol. 1:430, 1970.
  128. Nowell, P.C., Hirsch, B.E., Fox, D.H., Wilson, D.B. Evidence for the existence of multipotential lymphohematopoietic stem cells in the adult rat. J. Cell. Physiol. 75:151. 1970.
  129. Silvers, W.K., Lubaroff, D.M., Wilson, D.B., Fox, D.H. Mixed lymphocyte reactions and tissue transplantation tolerance. Science 167:1264-1264, 1970.
  130. Wilson, D.B. Immunological surveillance. Cell. Immunol. 1:245, 1970.
  131. Wilson, D.B. Immunological surveillance. Science 169:1006-1010, 1970. 
  132. Wilson, D.B. Immunospecific proliferation and antigen recognition. All India Institute Medical Sciences Bulletin 3:170, 1970.
  133. Wilson, D.B., Nowell, P.C. Quantitative studies on the mixed lymphocyte interaction in rats. IV. Immunologic potentiality of the responding cells. J. Exp. Med. 131:391, 1970.
  134. Wilson, D.B. Lymphocytes and the homograft reaction. In: Proceedings of the Scientific Sessions Marking the Centennial of the Faculty of Medicine, I.E. Parkis and U.F. Matthews, eds. Dalhousie University, Halifax, Nova Scotia, 1969.
  135. Wilson, D.B., Elkins, W.L. Proliferative interaction of lymphocytes in vitro and in vivo. Manifestations of immunologic competence. In: Proc. Third Annual Leukocyte Culture Conference, Iowa City, Iowa. W.O. Rieke, ed. Appleton-Century-Croft, pp. 391-407, 1969.
  136. Wilson, D.B., Nowell, P.C. Proportion of the immunologically reacting cells in the MLI. Fed. Proc. 28:380, 1969 (abstract). 
  137. Feldman, J.D., Pick, E., Lee, S., Silvers, W.K., Wilson, D.B. Renal homotransplantation in rats. II. Tolerant recipients. Am. J. Pathol. 52:687, 1968.
  138. Wilson, D.B. The immunologic significance of the lymphocyte with particular reference to transplantation immunity. In: Biology of the Immune Response. M. LaVia and P. Abramoff, eds., 1968.
  139. Wilson, D.B., Blyth, J., Nowell, P.C. The cell cycle time of mixed leukocyte interactions. Fed. Proc. 27:687, 1968 (abstract). 
  140. Wilson, D.B., Blyth, J.L., Nowell, P.C. Quantitative studies on the mixed lymphocyte interactions in rats. III. Kinetics on the response. J. Exp. Med. 128:1157, 1968.
  141. Silvers, W.K., Wilson, D.B., Palm, J.E. Mixed leukocyte reactions and histocompatibility in rats. Science 155:703-704, 1967.
  142. Silvers, W.K., Wilson, D.B., Palm, J.E. Typing and immunosuppression in rats. Transplantation 5:1053, 1967.
  143. Wilson, D.B. Lymphocytes as mediators of cellular immunity: Destruction of homologous target cells in culture. Transplantation 5:986, 1967.
  144. Wilson, D.B. Quantitative studies on the mixed lymphocyte interaction in rats. I. Conditions and parameters of response. J. Exp. Med. 126:625, 1967.
  145. Wilson, D.B., Billingham, R.E. Lymphocytes and transplantation immunity. Adv. Immunol. 7:189, 1967. 
  146. Wilson, D.B., Silvers, W.K., Nowell, P.C. Quantitation studies on the mixed lymphocyte interaction in rats. II. Relationship of the proliferative response to immunologic studies of the donors. J. Exp. Med. 126:655, 1967.
  147. Wilson, D.B. Analysis of some of the variables associated with the proliferative response of human lymphoid cells in culture. J. Exp. Zool. 162:161, 1966. 
  148. Wilson, D.B., Silvers, W.K., Billingham, R.E. Failure to transfer sensitivity to skin homografts by means of "immune" lymphoid cells in diffusion chambers. Nature 209:1359, 1966.
  149. Wilson, D.B., Wecker, E.E. Quantitative studies on the behavior of sensitized lymphocytes in vitro. III. Conversion of "normal" lymphoid cells to an immunologically active status with RNA derived from isologous lymphoid tissue of specifically immunized rats. J. Immunol. 97:512-516, 1966.
  150. Billingham, R.E., Silvers, W.K., Wilson, D.B. A second study in the H-Y transplantation antigen in mice. Proc. Royal Soc. London B 163:61-89, 1965. 
  151. Roosa, R.A., Wilson, D.B., Defendi, V. Effect of thymectomy on hamsters. Proc. Soc. Exp. Biol. Med. 118:584, 1965.
  152. Wilson, D.B. Discriminative enumeration of mixed anisometric cell populations with an electronic counter. Proc. Soc. Exp. Biol. Med. 119:728, 1965.
  153. Wilson, D.B. Quantitative studies on the behavior of sensitized lymphocytes in vitro. I. Relationship of the degree of destruction of homologous target cells to the number of lymphocytes and to the time of contact in culture and consideration of the effects of isoimmu J. Exp. Med. 122:143, 1965.
  154. Wilson, D.B. Quantitative studies on the behavior of sensitized lymphocytes in vitro. II. Inhibitory influence of the immune suppressor, imuran, on the destructive reaction of sensitized lymphoid cells against homologous target cells. J. Exp. Med. 122:167, 1965.
  155. Billingham, R.E., Silvers, W.K., Wilson, D.B. Further studies in adoptive transfer hypersensitivity to skin homografts. J. Exp. Med. 118:397, 1963.
  156. Roosa, R.A., Wilson, D.B., Defendi, V. Effect of neonatal thymectomy in hamsters. Fed. Proc. 22:599, 1963 (abstract).
  157. Wilson, D.B. Blood platelets and transplantation antigens. Transpl. 1:318, 1963.
  158. Wilson, D.B. Influence of host's sex on the induction of tolerance of homologous tissues. Transplantation 1:79, 1963.
  159. Wilson, D.B. The effect of immunologically activated lymphocytes on homologous cells in vitro. Fed. Proc. 22:275, 1963 (abstract).
  160. Wilson, D.B. The reaction of immunologically activated lymphoid cells against homologous target tissue cells in vitro. J. Cell. Comp. Physiol. 62:273, 1963. 
  161. Billingham, R.E., Silvers, W.K., Wilson, D.B. Adoptive transfer of transplantation immunity by means of blood borne cells. Lancet i:512, 1962. 
  162. Wilson, D.B. Methods of procuring thoracic duct lymphocytes. In: Transplantation of Tissues and Cells, R.E. Billingham and W.K. Silvers, eds. Wistar Institute Press, Philadelphia, Chapter 10, 1961.
  163. Wilson, D.B. Parabiosis. In: Transplantation of Tissues and Cells, R.E. Billingham and W.K. Silvers, eds. Wistar Institute Press, Philadelphia, Chapter 10, 1961.
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