Keith Bishop, Ph.D.
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.
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.
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, 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.
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.
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.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.