A number of different mechanisms exist to effect allograft rejection. The role of the lymphocyte is central in graft rejection; ample evidence exists that the helper T cell and the cytolytic T cell can effect graft loss. It is also clear that events occurring locally at the graft site are distinct from the systemic response to the allograft. The sponge matrix allograft model provides ready access to cells which accumulate at the site of allograft rejection. In combination with limiting dilution analysis which can identify small numbers of sensitized cells, we can readily assess events associated with local and systemic allograft immunity. Using these functional assessments of lymphocytes rather than radiolabel eliminates the need to introduce radiolabelled cells into the intravascular space. We plan to use these techniques to define these local and systemic events according to the tissue transplanted. Once these events are defined for various tissue we plan to use either local or systemic immunosuppression to modify them. The long term goal is to employ local immunosuppression to render the animal's systemic immune apparatus intact.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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University of California San Francisco
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Wacher, V J; Liu, T; Roberts, J P et al. (1995) Time course of cyclosporine and ist motabolites in blood, liver and spleen of naive Lewis rats: comparison with preliminary data obtained in transplanted animals. Biopharm Drug Dispos 16:303-12
Osorio, R W; Ascher, N L; Melzer, J S et al. (1994) beta-2 Microglobulin gene disruption prolongs murine islet allograft survival in NOD mice. Transplant Proc 26:752
Osorio, R W; Ascher, N L; Melzer, J S et al. (1994) Enhancement of islet allograft survival in mice treated with MHC class I specific F(ab')2 alloantibody. Transplant Proc 26:749
Osorio, R W; Ascher, N L; Stock, P G (1994) Prolongation of in vivo mouse islet allograft survival by modulation of MHC class I antigen. Transplantation 57:783-8
Martinez, O M; Villanueva, J C; Lake, J et al. (1993) IL-2 and IL-5 gene expression in response to alloantigen in liver allograft recipients and in vitro. Transplantation 55:1159-66
Osorio, R W; Ascher, N L; Jaenisch, R et al. (1993) Isolation of functional MHC class I-deficient islet cells. Transplant Proc 25:968-9
Osorio, R W; Ascher, N L; Jaenisch, R et al. (1993) Major histocompatibility complex class I deficiency prolongs islet allograft survival. Diabetes 42:1520-7
Martinez, O M; Ascher, N L; Ferrell, L et al. (1993) Evidence for a nonclassical pathway of graft rejection involving interleukin 5 and eosinophils. Transplantation 55:909-18
Krams, S M; Ascher, N L; Martinez, O M (1993) New immunologic insights into mechanisms of allograft rejection. Gastroenterol Clin North Am 22:381-400
Freise, C E; Clemmings, S; Clemens, L E et al. (1991) Demonstration of local immunosuppression with methylprednisolone in the sponge matrix allograft model. Transplantation 52:318-25

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