Abstract

The object of this program project is to apply new technological advances in basic immunology, the production of monoclonal antibodies and T cell clones to help develop protocols for the induction of tissue transplantation tolerance in humans. Our preliminary studies suggest that preparation of cadaver renal transplant recipients with total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) can markedly reduce, or perhaps eliminate, the requirement for chronic immunosuppressive drug therapy. The proposed project attempts to use mouse monoclonal antibodies to human T cells as new therapeutic agents (to replace the polyclonal rabbit ATG) and as new diagnostic agents (to monitor changes in T cell subsets). A variety of monoclonal antibodies to human T cells will be generated and analyzed for their capacity to identify new subsets which play important roles in transplantation immunity. We will study the mechanism of action of the suppressor cells and search for suppressive lymphokines. Cloned human suppressor cells will also be used as immunogens in order to generate mouse monoclonal antibodies to surface markers which are unique to these suppressor cell subpopulations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK032075-04
Application #
3095275
Study Section
Transplantation and Immunology Committee (TIC)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Seydel, K; Shizuru, J; Grossman, D et al. (1991) Anti-CD8 abrogates effect of anti-CD4-mediated islet allograft survival in rat model. Diabetes 40:1430-4
Alters, S E; Shizuru, J A; Ackerman, J et al. (1991) Anti-CD4 mediates clonal anergy during transplantation tolerance induction. J Exp Med 173:491-4
Shizuru, J A; Seydel, K B; Flavin, T F et al. (1990) Induction of donor-specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy. Transplantation 50:366-73
Koide, J; Engleman, E G (1990) Differences in surface phenotype and mechanism of action between alloantigen-specific CD8+ cytotoxic and suppressor T cell clones. J Immunol 144:32-40
Flavin, T; Shizuru, J; Seydel, K et al. (1990) Selective T-cell depletion with Ox-38 anti-CD4 monoclonal antibody prevents cardiac allograft rejection in rats. J Heart Transplant 9:482-8
Takada, S; Koide, J; Engleman, E G (1989) Differences in surface phenotype between cytolytic and non-cytolytic CD4+ T cells. MHC class II-specific cytotoxic T lymphocytes lack Leu 8 antigen and express CD2 in high density. J Immunol 142:3038-44
Trager, D K; Banks, B A; Rosenbaum, G E et al. (1989) Cardiac allograft prolongation in mice treated with combined posttransplantation total-lymphoid irradiation and anti-L3T4 antibody therapy. Transplantation 47:587-91
Strober, S; Dhillon, M; Schubert, M et al. (1989) Acquired immune tolerance to cadaveric renal allografts. A study of three patients treated with total lymphoid irradiation. N Engl J Med 321:28-33
Bender, J R; Pardi, R; Kosek, J et al. (1989) Evidence that cytotoxic lymphocytes alter and traverse allogeneic endothelial cell monolayers. Transplantation 47:1047-53
Saper, V; Chow, D; Engleman, E D et al. (1988) Clinical and immunological studies of cadaveric renal transplant recipients given total-lymphoid irradiation and maintained on low-dose prednisone. Transplantation 45:540-6

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