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Peritransplant VLA ‐4 blockade inhibits endogenous memory CD 8 T cell infiltration into high‐risk cardiac allografts and CTLA ‐4Ig resistant rejection
Author(s) -
Iida Shoichi,
Miyairi Satoshi,
Su Charles A.,
Abe Toyofumi,
Abe Ryo,
Tanabe Kazunari,
Dvoriina,
Baldwin William M.,
Fairchild Robert L.
Publication year - 2019
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.15147
Subject(s) - alloimmunity , infiltration (hvac) , cd8 , medicine , immunology , inflammation , t cell , cytotoxic t cell , endogeny , priming (agriculture) , blockade , cancer research , antigen , biology , immune system , receptor , physics , germination , botany , thermodynamics , biochemistry , in vitro
Recipient endogenous memory CD 8 T cells expressing reactivity to donor class I MHC infiltrate MHC ‐mismatched cardiac allografts within 24 hours after reperfusion and express effector functions mediating graft injury. The current study tested the efficacy of Very Late Antigen‐4 ( VLA ‐4) blockade to inhibit endogenous memory CD 8 T cell infiltration into cardiac allografts and attenuate early posttransplant inflammation. Peritransplant anti‐ VLA ‐4 mA b given to C57 BL 6 (H‐2 b ) recipients of AJ (H‐2 a ) heart allografts completely inhibited endogenous memory CD 4 and CD 8 T cell infiltration with significant decrease in macrophage, but not neutrophil, infiltration into allografts subjected to either minimal or prolonged cold ischemic storage ( CIS ) prior to transplant, reduced intra‐allograft IFN ‐γ‐induced gene expression and prolonged survival of allografts subjected to prolonged CIS in CTLA ‐4Ig treated recipients. Anti‐ VLA ‐4 mA b also inhibited priming of donor‐specific T cells producing IFN ‐γ until at least day 7 posttransplant. Peritransplant anti‐ VLA plus anti‐ CD 154 mA b treatment similarly prolonged survival of allografts subjected to minimal or increased CIS prior to transplant. Overall, these data indicate that peritransplant anti‐ VLA ‐4 mA b inhibits early infiltration memory CD 8 T cell infiltration into allografts with a marked reduction in early graft inflammation suggesting an effective strategy to attenuate negative effects of heterologous alloimmunity in recipients of higher risk grafts.