Donor-Reactive CD8 Memory T Cells Infiltrate Cardiac Allografts Within 24-h Posttransplant in Naive Recipients |
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Authors: | A. D. Schenk T. Nozaki M. Rabant A. Valujskikh R. L. Fairchild |
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Affiliation: | Department of Pathology, Case Western Reserve University, Cleveland, OH;Glickman Urological Institute and Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH;Department of Urology, Tokyo Women's Medical School, Tokyo, Japan;Service de Transplantation Rénale, Hôpital Necker, Cedex 15, France |
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Abstract: | 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. |
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Keywords: | CD8 memory T cells graft infiltration IFN-γ |
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