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IL‐15 Induces Alloreactive CD28 − Memory CD8 T Cell Proliferation and CTLA4‐Ig Resistant Memory CD8 T Cell Activation
Author(s) -
Traita O.,
Gorbachev A.,
Bechtel J. J.,
Keslar K. S.,
Baldwin W. M.,
Poggio E. D.,
Fairchild R. L.
Publication year - 2014
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/ajt.12719
Subject(s) - medicine , cytotoxic t cell , memory t cell , cd8 , t cell , microbiology and biotechnology , cancer research , immunology , immune system , biology , genetics , in vitro
The presence of CD28 − memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA‐4Ig induction therapy. In vitro analyses have indicated poor alloantigen‐induced CD28 − memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28 − memory CD8 T cell proliferation. Addition of IL‐15, but not IL‐2 or IL‐7, to co‐cultures of CD28 − or CD28 + memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28 − and enhanced CD28 + memory T cell proliferation. Proliferating CD28 − memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28 + memory CD8 T cells. CTLA‐4Ig inhibited alloantigen‐induced proliferation of CD28 + memory CD8 T cell proliferation but had no effect on alloantigen plus IL‐15‐induced proliferation of either CD28 − or CD28 + memory CD8 T cells. These results indicate the ability of IL‐15, a cytokine produced by renal epithelial during inflammation, to provoke CD28 − memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA‐4Ig‐mediated costimulation blockade.