Date: Sunday, May 3, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 4:12pm-4:24pm
Location: Room 120-ABC
Endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts and produce IFN-γ in response to donor class І MHC within 24 hrs after graft reperfusion in mice. Our recent studies indicate that prolonged cold ischemic graft storage provokes intense inflammation within hours after allograft reperfusion and promotes endogenous memory CD8 T cell accumulation that leads to rejection of the allograft. Mechanisms underlying the accumulation of endogenous memory CD8 T cells in highly ischemic cardiac allografts were investigated. Complete MHC-mismatched C57BL/6 (H-2b) hearts were subjected to minimal 0.5 hrs or 8 hrs of cold ischemic storage in University of Wisconsin solution and then transplanted to A/J (H-2a) mice. Using BrdU pulsing of recipients of minimally and highly ischemic allografts, proliferation of endogenous memory CD4 and CD8 T cells was increased 2-3-fold in highly ischemic vs. minimally ischemic grafts when assessed 48 hours after transplantation. Treating recipients with cyclophosphamide inhibited this memory T cell proliferation and accumulation within the allograft. Highly ischemic cardiac allografts deficient in expression of class II MHC or CD40 had marked decreases in endogenous memory CD4 and CD8 T cell proliferation and accumulation within the allograft. In addition, highly ischemic cardiac allografts expressing a single class I MHC disparity had marked decreases in endogenous memory CD8 T cell proliferation and accumulation within the allograft. These studies suggest an intricate series of signals required to promote the proliferation of endogenous memory CD8 T cells within cardiac allografts subjected to prolonged cold ischemic storage and their function in directly mediating graft rejection.
To cite this abstract in AMA style:Tanaka T, Tsuda H, Kohei N, Kish D, Baldwin W, Valujskikh A, Fairchild R. Allograft Class II MHC and CD40 Expression Are Required for Endogenous Memory CD8 T Cell Proliferation in Cardiac Allografts Subjected to Prolonged Cold Ischemic Storage [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/allograft-class-ii-mhc-and-cd40-expression-are-required-for-endogenous-memory-cd8-t-cell-proliferation-in-cardiac-allografts-subjected-to-prolonged-cold-ischemic-storage/. Accessed April 19, 2021.
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