In the previous grant period (12/01/83 - 12/31/85), we have established antigen-specific as well as nonspecific suppressor T cell hybridoma lines and characterized functional properties of their culture supernatant. The objectives of our current proposal are to obtain a highly purified, potent suppressor lymphokine(s) and to use it in vivo as a specific immunosuppressive reagent to induce allograft unresponsiveness. More specifically, the experiments described herein are designed 1) to further analyse physicochemical properties of the suppressor lymphokine with the use of various protein separation techniques; this study will provide information which is essential for the subsequent purification of highly potent, functionally defined suppressor lymphokine, 2) to investigate the mechanism(s) of suppression by binding studies and with the use of immune affinity chromatography, 3) to produce monoclonal antibodies reactive with the suppressor lymphokine, and 4) to establish optimal conditions for in vivo use of purified suppressor lymphokine in order to induce prolongation of allograft survival. We believe that the results obtained from these studies will provide important information for the establishment of better and more specific immunosuppressive therapy in clinical transplantation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020686-06
Application #
3130491
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-12-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
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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