MHC class II molecules on graft endothelium promote acute rejection

A limitation of organ transplant is acute rejection of the graft by the host immune system. Graft rejection is mediated by the development of CD8⁺ cytotoxic T cells that target donor MHC class I molecules, and in animal models, these cells have been shown to develop in secondary lymphoid organs. However, in humans, there is evidence that cytotoxic T cells mature within the graft without trafficking to secondary sites. A new study in the inaugural issue of JCI Insight indicates that the development of graft-targeting CD8⁺ cytotoxic T cells requires CD4⁺ effector memory T cells. Specifically, Jordan Pober and colleagues at Yale University used a mouse model in which human artery segments are grafted into immunodeficient mice followed by adoptive transfer of human T cells that are allogenic to the graft. Using this model, the researchers determined that CD4⁺ effector memory T cells are activated by MHC class II molecules on graft endothelial cells and promote development of graft-targeting CD8⁺ cytotoxic T cells. Moreover, eliminating class II MHC expression on endothelial cells prevented CD8⁺ T effector memory cell responses. The results of this study indicate that blocking interactions between CD4⁺ effector memory T cells and class II MHC molecules should be further explored as a potential intervention to limit acute rejection.

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TITLE: Blocking MHC class II on human endothelium mitigates acute rejection

AUTHOR CONTACT: Jordan Pober
Yale University School of Medicine
Department of Immunobiology
10 Amistad St
New Haven, CT 06520-8089 USA
Email: jordan.pober@yale.edu

View this article at: http://insight.jci.org/articles/view/85293

JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight go to http://www.insight.jci.org.