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.
Source: Journal of Clinical Investigation