TY - JOUR
T1 - Critical role for CD8+ T cells in allograft acceptance induced by DST and CD40/CD154 costimulatory blockade
AU - Gao, Donghong
AU - Lunsford, Keri E.
AU - Eiring, Anna M.
AU - Bumgardner, Ginny L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
KW - Alloantibody
KW - CD8T lymphocytes
KW - Co-stimulation
KW - Donor specific transfusion
KW - Graft acceptance
KW - Hepatocytes
KW - Lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=3042783209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042783209&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2004.00490.x
DO - 10.1111/j.1600-6143.2004.00490.x
M3 - Article
C2 - 15196062
AN - SCOPUS:3042783209
VL - 4
SP - 1061
EP - 1070
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 7
ER -