Immunology Graduate Group

Bruce R. Rosengard, M.D.
Department of Surgery

Address: 6 Silverstein Pavilion (office)
352 Stemmler (lab)
Office Phone: 215-662-4765
Lab Phone: 215-662-2018
Email: brosenga@mail.med.upenn.edu

Education:
B.S., Biology, Chemistry, Tufts University
M.D., The Johns Hopkins University School of Medicine
Postdoctoral Fellowship in Transplantation Immunology, N.C.I., N.I.H.

Research Interests

Immunological Tolerance, Chronic Rejection, Xenotransplantation

Research Summary

Our laboratory is primarily interested in the role that bone marrow-derived antigen presenting cells and endothelial cells play in triggering both acute and chronic rejection of solid organ grafts.Ê Our approach has been to use bone marrow transplantation to create chimeric organs, so that we can control the characteristics of professional antigen presenting cells and/or graft endothelium and parenchyma.Ê We have studied these chimeric grafts in murine models of heart and liver transplantation.Ê Thus far, we have demonstrated that: (1) donor-type APCs play an important role in triggering acute, but not chronic rejection in heart grafts; (2) bone marrow-derived APCs are required for liver allograft tolerance, although the phenomenon is not mediated by solely by donor-type APCs, as recipient-type or third party APCs permit tolerance induction; and (3) endothelium does not play a significant role in triggering acute cardiac allograft rejection in vivo (Figure 1).Ongoing studies are focused on the role of endothelium in triggering of cardiac allograft vasculopathy (chronic cardiac rejection) and defining the allorecognition pathways responsible for this pathological process.

A second area of interest is xenotransplantation.We are characterizing the mechanisms of human anti-pig cellular responses in vitro, with particular focus on whether allosensitization leads to heightened cell-mediated xeno-immunity. In addition, we are conducting transgenic pig-to-baboon kidney transplants to study the pathogenesis of acute vascular xenograft rejection.The pigs are transgenic for Decay Accelerating Factor, a species-restricted regulator of complement activation, which prevents immediate hyperacute rejection.

The role of the donor endothelium in acute cardiac rejection: A. MHC Class II sufficient APCs. C3H mice received hearts from either autologously reconstituted B6(B6) BMT mice (n = 11) or chimeric B6II-(B6) BMT mice (n = 5). B. MHC Class II deficient APCs. C3H mice received hearts from either B6II- mice (n = 9) or chimeric B6(B6II-) BMT mice (n = 8). These data demonstrate that the tempo of acute rejection is not altered by endothelial Class II expression. Thus, endothelium plays a minor role in triggering acute rejection via the CD4+ direct pathway.

 

Biomedical Graduate Studies | University of Pennsylvania | Contact