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

Content Provider	PubMed Central
Author	Chen, Yifa Demir, Yilmaz Anna, Valujskikh Heeger, Peter S.
Copyright Year	2004
Abstract	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.
Related Links	http://dx.doi.org/10.1016/s0002-9440(10)63227-0
Ending Page	1415
Page Count	9
Starting Page	1407
File Format	PDF
ISSN	00029440
e-ISSN	15252191
Journal	The American Journal of Pathology
Issue Number	4
Volume Number	164
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	2004-04-01
Access Restriction	Open
Rights Holder	American Society for Investigative Pathology
Subject Keyword	Pathology and Forensic Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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