Session Name: Concurrent Session: Immune Regulation and Graft Survival
Date: Monday, May 4, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 4:48pm-5:00pm
Location: Room 119-B
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 CTLA-4Ig-resistant endogenous memory CD8 T cell rejection of the allograft by day 28 post-transplant (whereas CTLA-4Ig prolongs survival of allografts subjected to minimal ischemic storage > day 60). This study tested the ability of strategies inhibiting endogenous memory CD8 T cell infiltration into cardiac allografts subjected to prolonged cold ischemic storage to promote long-term allograft survival. Peri-transplant anti-LFA-1 mAb and anti-CD154 mAb treatment of recipients of allografts subjected to minimal cold ischemic storage prolonged survival of 60% of the allografts > 100 days. In contrast, this treatment prolonged only 20% of allografts subjected to prolonged cold ischemic storage beyond day 80 post-transplant, with rejection accompanied by the appearance of high titers of donor-specific antibody (>10,000 vs. <100 in long-term survivors). Use of a newly devised regimen: peri-transplant treatment of recipients with anti-LFA-1 mAb, anti-TNFα mAb, and anti-CD154 mAb plus additional doses of anti-CD154 mAb on days 14 and 16 post-transplant promoted long-term survival of 60% allografts subjected to prolonged cold ischemic storage past day 100 post-transplant. On day 100 post-transplant these surviving allografts had strong beating and recipients had low numbers of donor-reactive CD4 and CD8 T cells producing IFN-γ in the spleen. These studies indicate the ability to promote long-term survival of allografts subjected to prolonged ischemic storage by devising strategies that include reagents inhibiting endogenous memory CD8 T cell infiltration into the allografts and reagents that inhibit the production of DSA.
To cite this abstract in AMA style:Kohei N, Tsuda H, Tanaka T, Iida S, Abe T, Su C, Kish D, Tanabe K, Valujskikh A, Fairchild R. Inhibition of Endogenous Memory CD8 T Cell Infiltration Into Cardiac Allografts Subjected to Prolonged Cold Ischemic Storage Is Required to Promote Long-Term Graft Survival [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/inhibition-of-endogenous-memory-cd8-t-cell-infiltration-into-cardiac-allografts-subjected-to-prolonged-cold-ischemic-storage-is-required-to-promote-long-term-graft-survival/. Accessed June 23, 2021.
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