Premium
Critical Role for CD8 + T Cells in Allograft Acceptance Induced by DST and CD40/CD154 Costimulatory Blockade
Author(s) -
Gao Donghong,
Lunsford Keri E.,
Eiring Anna M.,
Bumgardner Ginny L.
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00490.x
Subject(s) - cd154 , cd8 , immunotherapy , medicine , blockade , immunology , cytotoxic t cell , monoclonal antibody , cancer research , cd40 , immune system , biology , antibody , receptor , biochemistry , in vitro
Donor‐specific transfusion (DST) and CD40/CD154 costimulation blockade is a powerful immunosuppressive strategy which prolongs survival of many allografts. The efficacy of DST and anti‐CD154 mAb for prolongation of hepatocellular allograft survival was only realized in C57BL/6 mice that have both CD4‐ and CD8‐dependent pathways available (median survival time, MST, 82 days). Hepatocyte rejection in CD8 KO mice which is CD4‐dependent was not suppressed by DST and anti‐CD154 mAb treatment (MST, 7 days); unexpectedly DST abrogated the beneficial effects of anti‐CD154 mAb for suppression of hepatocyte rejection (MST, 42 days) and on donor‐reactive alloantibody production. Hepatocyte rejection in CD4 KO mice which is CD8‐dependent was suppressed by treatment with DST and anti‐CD154 mAb therapy (MST, 35 days) but did not differ significantly from immunotherapy with anti‐CD154 mAb alone (MST, 32 days). Induction of hepatocellular allograft acceptance by DST and anti‐CD154 mAb immunotherapy was dependent on host CD8 + T cells, as demonstrated by CD8 depletion studies in C57BL/6 mice (MST, 14 days) and CD8 reconstitution of CD8 KO mice (MST, 56 days). These studies demonstrate that both CD4 + and CD8 + T‐cell subsets contribute to induction of hepatocellular allograft acceptance by this immunotherapeutic strategy.