Posttransplant inflammation promotes memory T cell recovery following antibody-mediated lymphoablation (TRAN3P.900)

Abstract

Abstract Antibody-mediated depletion is commonly used as an induction therapy in recipients of organ transplants subjected to prolonged cold ischemia. We tested how surgery-induced inflammation and ischemia/reperfusion injury affect the recipient T cell recovery after lymphoablation. We previously reported that preexisting memory T cells rapidly expand and mediate rejection in B6 recipients of BALB/c heart allografts treated with murine antithymocyte globulin (mATG). Memory CD8 T cell recovery was not influenced by specificity for donor alloantigens suggesting a role for posttransplant inflammation. In support of this, CD8 T cells recovered faster in B6 isograft recipients than in non-transplanted mice treated with mATG. The increase in cold ischemic time from 0.5 h to 8 h markedly enhanced the post-depletion expansion of memory CD8 T cells in allograft recipients (10 fold increase at d. 10 posttransplant). Treatment with neutralizing anti-TNFα Ab decreased the numbers of donor-reactive IFNγ producing cells in the spleens of mATG treated heart allograft recipient by 60%, but had little effect on the anti-donor responses in control IgG treated recipients suggesting that TNFα facilitates T cell recovery rather than priming. Our data show that posttransplant inflammation facilitates memory T cell reconstitution following antibody-mediated depletion and that neutralizing proinflammatory cytokines may improve the efficacy of induction therapies in sensitized transplant recipients.