In our preliminary studies, we have established the basic hybridization technique to obtain suppressor T cell hybridomas which produce alloantigen specific and nonspecific suppressor factors. The objectives of the current proposal are 1) to further establish antigenspecific andnonspecific suppressor T cell hybridoma lines using somatic cell hybridization techniques and suppressor T cells obtained from mice unresponsive to skin allografts, 2) to determine the in vitro functions of the hybridoma-derived suppressor factors by mixed lymphocyte cultures and cell-mediated cytotoxicity assays, 3) to characterize the nature of these suppressor factors by immunochemical and physico-chemical analyses, and 4) to assess the capacity of these suppressor factors to prolong skin allograft survival in vivo. We believe that the information obtained from the proposed experiments, when coupled with our previous results, should provide insight into the nature of T cell receptors for alloantigens and the mechanisms responsible for the regulation of cell-cell interactions in allograft unresponsiveness. It is also hoped that such hybridoma lines would serve as a constant source of biologically active suppressor factors which could be used as a biological immunosuppressive reagent for the induction or maintenance of allograft unresponsiveness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020686-02
Application #
3130488
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Yanagie, H; Takeda, Y; Maki, T (1993) In vitro and in vivo activities of long-term cultured veto suppressor clones. Transplant Proc 25:350-1
Ohzato, H; Porter, J; Monaco, A P et al. (1993) Fifty islets maintain euglycemia and survive longer than 200 islets in allogeneic and xenogeneic diabetic hosts. Transplant Proc 25:953-4
Takeda, Y; Yanagie, H; Maki, T (1993) Cloned veto cells as immunoregulators. Transplant Proc 25:2743-4
Takahashi, T; Mafune, K; Maki, T (1990) Cloning of self-major histocompatibility complex antigen-specific suppressor cells from adult bone marrow. J Exp Med 172:901-9
Kanai, T; Porter, J; Monaco, A P et al. (1989) Successful treatment of experimental diabetes by sequential transplantations of multiple-donor pancreatic islet allografts. Transplantation 47:3-6
Kanai, T; Porter, J; Gotoh, M et al. (1989) Effect of gamma-irradiation on mouse pancreatic islet-allograft survival. Diabetes 38 Suppl 1:154-6
Gotoh, M; Porter, J; Kanai, T et al. (1988) Multiple donor allotransplantation. A new approach to pancreatic islet transplantation. Transplantation 45:1008-12
Gotoh, M; Porter, J; Monaco, A P et al. (1988) Induction of antigen-specific unresponsiveness to pancreatic islet allografts by antilymphocyte serum. Transplantation 45:429-33
Gotoh, M; Maki, T; Satomi, S et al. (1987) Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic ductal or portal venous collagenase injection. Transplantation 43:725-30
Gotoh, M; Maki, T; Porter, J et al. (1987) Pancreatic islet transplantation using H-2 incompatible multiple donors. Transplant Proc 19:957-9

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