This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Heeger, P. S. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Heeger, P. S.

(American Journal of Pathology. 2004;164:1407-1415.)
© 2004 American Society for Investigative Pathology

Antigen Location Contributes to the Pathological Features of a Transplanted Heart Graft

Yifa Chen^*, Yilmaz Demir^*, Anna Valujskikh^* and Peter S. Heeger^*

From the Department of Immunology^*and The Glickman Urologic Institute,the Cleveland Clinic Foundation, Cleveland; and the Institute of Pathology,Case Western Reserve University, Cleveland, Ohio

Organ-specific injury after transplantation presents with a variety of clinical and pathological phenotypes, yet the factors influencing development of each outcome are poorly understood. Because primed T lymphocytes must re-encounter their antigen within the target organ to engage effector functions, we postulated that the cellular location of antigen within that organ could significantly impact the induced pathology. We challenged female Marilyn CD4 T-cell receptor transgenic mice, in which all T cells are specific for the male minor transplantation antigen, with male heart transplants expressing the relevant peptide: major histocompatibility complex on either graft parenchymal/vascular cells or alternatively, on graft-infiltrating mononuclear cells. The two different graft donors led to equivalent activation of recipient T cells as assessed by frequency, cell surface marker expression, cytokine production, and the ability to traffic to the graft. Nonetheless, if the target antigen was expressed on graft vascular and/or parenchymal cells, the outcome was acute graft destruction. In contrast, if the antigen was expressed only on graft-infiltrating mononuclear cells the same effector T-cell repertoire caused chronic rejection and vasculopathy. This unique result, that target antigen location can influence pathological outcome, has significant implications for understanding the pathogenesis of chronic allograft injury in humans.

This article has been cited by other articles:

				P. N. Lalli, M. G. Strainic, F. Lin, M. E. Medof, and P. S. Heeger Decay Accelerating Factor Can Control T Cell Differentiation into IFN-{gamma}-Producing Effector Cells via Regulating Local C5a-Induced IL-12 Production J. Immunol., November 1, 2007; 179(9): 5793 - 5802. [Abstract] [Full Text] [PDF]

				A. Valujskikh, Q. Zhang, and P. S. Heeger CD8 T Cells Specific for a Donor-Derived, Self-Restricted Transplant Antigen Are Nonpathogenic Bystanders after Vascularized Heart Transplantation in Mice J. Immunol., February 15, 2006; 176(4): 2190 - 2196. [Abstract] [Full Text] [PDF]

				Q. Zhang, Y. Chen, R. L. Fairchild, P. S. Heeger, and A. Valujskikh Lymphoid Sequestration of Alloreactive Memory CD4 T Cells Promotes Cardiac Allograft Survival J. Immunol., January 15, 2006; 176(2): 770 - 777. [Abstract] [Full Text] [PDF]

				C. E. Ruiz, M. Iemura, S. Medie, P. Varga, W. G. Van Alstine, S. Mack, A. Deligio, N. Fearnot, U. H. Beier, D. Pavcnik, et al. Transcatheter placement of a low-profile biodegradable pulmonary valve made of small intestinal submucosa: A long-term study in a swine model J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 477 - 484. [Abstract] [Full Text] [PDF]

				R. Bagai, A. Valujskikh, D. H. Canaday, E. Bailey, P. N. Lalli, C. V. Harding, and P. S. Heeger Mouse Endothelial Cells Cross-Present Lymphocyte-Derived Antigen on Class I MHC via a TAP1- and Proteasome-Dependent Pathway J. Immunol., June 15, 2005; 174(12): 7711 - 7715. [Abstract] [Full Text] [PDF]