Abstract

It is proposed to examine the cellular and molecular mechanisms by which vascularized organ allografts are rejected or accepted. A state of specific unresponsiveness towards transplant antigens in rats will be elucidated. The subpopulation(s) of suppressor cells will be identified with monoclonal antibodies. Their specific role will be explored in the adoptive transfer assay and in novel assays. Their reactivity against alloantigen or idiotype, as well as the role of MCH antigen release in the specifically unresponsiveness state will be examined. New techniques to illuminate the suppressor response will include culture and cloning of the suppressor cells, in vitro induction of cells that either induce or effect the response, and assay and mRNA analysis of lymphokines that facilitate the unresponsive state. To determine the variable induction of unresponsiveness among various strains, the rejection, reaction and suppressor cells from such strains will be compared using in vivo and in vitro systems. Better characterization of suppressor mechanisms should permit (1) the development of in vitro assays to detect unresponsiveness in transplanted patients, thereby minimizing the need for non- specific immunosuppression; and (2) Strategies to induce suppressor responses in clinical transplantation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026041-03
Application #
3139660
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-03-01
Project End
1991-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
3
Fiscal Year
1990
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

Plain, Karren M; Boyd, Rochelle; Verma, Nirupama D et al. (2007) Transplant tolerance associated with a Th1 response and not broken by IL-4, IL-5, and TGF-beta blockade or Th1 cytokine administration. Transplantation 83:764-73
Aversa, G; Waugh, J A; Hall, B M (1994) A monoclonal antibody (A6) recognizing a unique epitope restricted to CD45RO and RB isoforms of the leukocyte common antigen family identifies functional T cell subsets. Cell Immunol 158:314-28
Pearce, N W; Spinelli, A; Gurley, K E et al. (1993) Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. V. Dependence of CD4+ suppressor cells on the presence of alloantigen and cytokines, including interleukin 2. Transplantation 55:374-80
Nicolls, M R; Aversa, G G; Pearce, N W et al. (1993) Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. Transplantation 55:459-68
Pearce, N W; Berger, M F; Gurley, K E et al. (1993) Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. VI. In vitro alloreactivity of T cell subsets from rats with long-surviving allografts. Transplantation 55:380-9
Quiza, C G; Leenaerts, P L; Hall, B M (1992) The role of T cells in the mediation of glomerular injury in Heymann's nephritis in the rat. Int Immunol 4:423-32
Quiza, C G; Leenaerts, P L; Hall, B M (1991) Induction of unresponsiveness to Heymann's nephritis: inhibited by monoclonal antibody to CD4 but not to CD8. Cell Immunol 133:456-67
Aversa, G G; Hall, B M (1991) Memory T cells express high levels of a novel leukocyte common antigen epitope identified by the A6 MAb. Transplant Proc 23:300-1
Hall, B M (1991) Cells mediating allograft rejection. Transplantation 51:1141-51
Hall, B M; Pearce, N W; Gurley, K E et al. (1990) Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action. J Exp Med 171:141-57

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