Critical role for CD8+ T cells in allograft acceptance induced by DST and CD40/CD154 costimulatory blockade

Donghong Gao, Keri E. Lunsford, Anna M. Eiring, Ginny L. Bumgardner

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1061-1070
Number of pages10
JournalAmerican Journal of Transplantation
Volume4
Issue number7
DOIs
StatePublished - Jul 2004

Keywords

  • Alloantibody
  • CD8T lymphocytes
  • Co-stimulation
  • Donor specific transfusion
  • Graft acceptance
  • Hepatocytes
  • Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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