Keith Bishop, Ph.D.
Professor, Department of Surgery
kbishop@umich.edu

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 the mouse vascularized cardiac allograft model. Emphasis is placed on the role of inductive cytokines (IL-12, IFN gamma, IL-4, IL-10, IL-6 and TGFβ) which influence the balance between Th1, Th2, and Th17 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 cardiac 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 or chronic allograft rejection.

Representative 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 TGFβ1 in vascularized cardiac allografts: Differential sensitivity of CD4+ and CD8+ T cells to TGFβ1. 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. 5:2378-2384.

Csencsits, K., S.C. Wood, G. Lu, S.M. Faust, D. Brigstock, E.J. Eichwald, C.G. Orosz, and D.K. Bishop. 2006. Transforming growth factor beta-induced connective tissue growth factor and chronic allograft rejection. Amer. J. Transplant. 6:959-966.

B.E. Burrell, K. Csencsits, G. Lu, S. Grabauskiene, and D.K. Bishop. 2008. CD8+ Th17 mediate costimulation blockade resistant allograft rejection in T-bet deficient mice. J Immunol . 2008 Sep 15; 181(6): 3906-14.

Wood, S.C., G. Lu, B.E. Burrell, and D.K. Bishop. 2008. Transplant acceptance following anti-CD4 versus anti-CD40L therapy: evidence for differential maintenance of graft-reactive T cells. Am J Transplant. 2008 Oct; 8 (10): 2037-48.

Csencsits, K., B.E. Burrell, G. Lu, E.J. Eichwald, G.L. Stahl, and D.K. Bishop. 2008. The classical complement pathway in transplantation: Unanticipated protective effects of C1q and role in inductive antibody therapy. Amer. J. Transplant., Aug; 8 ( 8 ): 1622-30.

Burrell, B.E., G. Lu, X.C. Li, and D.K. Bishop. 2009. OX40 costimulation prevents allograft acceptance induced by CD40-CD40L blockade. J. Immunol. 182:379-390.

Diaz, J.A., A.J. Booth, G. Lu, S.C. Wood, D.J. Pinsky, and D.K. Bishop. 2009. Critical role for IL-6 in hypertrophy and fibrosis in chronic cardiac allograft rejection. Amer. J. Transplant. 9:1773-1783.

Faust, S.M., G. Lu, B.L. Marini, W. Zou, D. Gordon, Y. Iwakura, Y, Laouar, and D.K. Bishop. 2009. Role of T cell TGFβ signaling and IL-17 in allograft acceptance and fibrosis associated with chronic rejection. J. Immunol. 183:7297-7306.

Faust, S.M., G. Lu, S.C. Wood, and D.K. Bishop. 2009. TGFβ neutralization within cardiac allografts by decorin gene transfer attenuates chronic rejection. J. Immunol. 183:7307-7313.

Booth, A.J., K. Csencsits-Smith, S.C. Wood, G. Lu, K.E. Lipson, and D.K. Bishop. 2010. Connective tissue growth factor promotes fibrosis downstream of TGFβ and IL-6 in chronic cardiac allograft rejection. Amer. J. Transplant. 10:220-230.

Booth, A.J., S. Grabauskiene, S.C. Wood, G. Lu, B.E. Burrell, and D.K. Bishop.  2011.  IL-6 promotes cardiac graft rejection mediated by CD4+ cells.  J. Immunol. 187:5764-5771.

Booth, A.J., S.C. Wood, A.M. Cornett, A.A. Dreffs, G. Lu, A.F. Muro, E.S. White, and D.K. Bishop.  2012.  Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.  J. Pathol. 226:609-618.