Faculty

Cellular Immunology of Transplant Rejection and Acceptance

     Our research is focused on identifying key regulatory events that influence T cell mediated immunity in vivo. This includes an analysis of cytokine regulation of effector cell development and the functional activities of T cells that culminate in tissue damage.

     These studies are conducted primarily in transplantation systems, including the immediately vascularized mouse cardiac allograft model. Emphasis is placed on the role of inductive cytokines (IL-12, gamma IFN, IL-4, IL-10, and TGF beta) which influence the balance between Th1 and Th2 helper T lymphocytes and the role of the CD40 - CD40 ligand costimulatory pathway in the subsequent development of deleterious versus tolerogenic immune responses.

     We have adapted the vascularized mouse heart transplant model for in situ gene transfer studies to assess the effects of local expression of immunosuppressive genes on systemic immune responses that lead to acute allograft rejection. This gene transfer strategy is also employed to define interactions between TGF beta, connective tissue growth factor, decorin, and the cyclin dependent kinase inhibitor p21 in the development of chronic allograft rejection. 

Selected Publications: 

     Chan, S.Y., K. Li, J.R. Piccotti, M.C. Louie, T.A. Judge, L.A. Turka, E.J. Eichwald, and D.K. Bishop. 1999. Tissue specific consequences of the anti-adenoviral immune response: Implications for cardiac transplants. Nature Medicine 5:1143-1149 . 

     Chan, S.Y., R.E. Goodman, J.R. Szmuskovicz, B. Roessler, E.J. Eichwald, and D.K. Bishop. 2000. Rapid Communication: DNA-liposome versus adenoviral mediated gene transfer of TGF b 1 in vascularized cardiac allografts: Differential sensitivity of CD4+ and CD8+ T cells to TGF b 1. Transplantation 70:1292-1301. 

     Bishop, D.K., S.Y. Chan, E.J. Eichwald, and C.G. Orosz. 2001. Immunobiology of allograft rejection in the absence of interferon-gamma: CD8+ effector cells develop independent of CD4+ cells and CD40 - CD40L interactions. J. Immunol. 166:3248-3255 . 

     Nathan, M.J., D. Yin, E.J. Eichwald, and D.K. Bishop. 2002. The immunobiology of inductive anti-CD40L therapy in transplantation: Allograft acceptance is not dependent upon the deletion of graft-reactive T cells. Amer. J. Transplant. 2:323-332 . 

     Csencsits, K. and D.K. Bishop. 2003. Contrasting alloreactive CD4+ and CD8+ cells: There's more to it than MHC restriction. Amer. J. Transplant. 3:107-115 . 

     Nathan, M.J., J.E. Mold, S.C. Wood, G. Lu, E.J. Eichwald, and D.K. Bishop. 2004. Requirements for donor and recipient CD40 expression in cardiac allograft rejection: Induction of Th1 responses and influence of donor-derived dendritic cells. J. Immunol. 172:6626-6633 .

     Csencsits, K., S.C. Wood, J.C. Magee, E.J. Eichwald, C.-H. Chang, and D.K. Bishop. 2005. Graft rejection following indirect presentation of donor alloantigen is associated with a dominant Th2 response. Eur. J. Immunol. 35:843-851.

     Csencsits, K., S.C. Wood, G. Lu, and D.K. Bishop. 2005. Transforming growth factor-beta1 gene transfer is associated with the development of regulatory cells. Amer. J. Transplant. (In Press).