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Donor‐Reactive CD8 Memory T Cells Infiltrate Cardiac Allografts Within 24‐h Posttransplant in Naive Recipients
Author(s) -
Schenk A. D.,
Nozaki T.,
Rabant M.,
Valujskikh A.,
Fairchild R. L.
Publication year - 2008
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.1600-6143.2008.02302.x
Subject(s) - alloimmunity , cytotoxic t cell , immunology , cd8 , antigen , medicine , immune system , major histocompatibility complex , t cell , memory t cell , biology , in vitro , biochemistry
Normal immune responses stimulated by pathogenic and environmental antigens generate memory T cells that react with donor antigens and no currently used immunosuppressive drug completely inhibits memory T‐cell function. While donor‐reactive memory T cells clearly compromise graft outcomes, mechanisms utilized by memory T cells to promote rejection are largely unknown. In this study, we investigated how early endogenous memory cells infiltrate and express effector function in cardiac allografts. Endogenous CD8 memory T cells in nonsensitized recipients distinguish syngeneic versus allogeneic cardiac allografts within 24 h of reperfusion. CD8‐dependent production of IFN‐γ and CXCL9/Mig was observed 24 to 72 h posttransplant in allografts but not isografts. CXCL9 was produced by donor cells in response to IFN‐γ made by recipient CD8 T cells reactive to donor class I major histocompatibility complex (MHC) molecules. Activated CD8 T cells were detected in allografts at least 3 days before donor‐specific effector T cells producing IFN‐γ were detected in the recipient spleen. Early inflammation mediated by donor‐reactive CD8 memory T cells greatly enhanced primed effector T‐cell infiltration into allografts. These results suggest that strategies for optimal inhibition of alloimmunity should include neutralization of infiltrating CD8 memory T cells within a very narrow window after transplantation.