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CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival

F. D’Addio,T. Ueno,M. Clarkson,Baogong Zhu,A. Vergani,G. Freeman,M. Sayegh,M. Ansari,P. Fiorina,A. Habicht

Published 2013 in PLoS ONE

ABSTRACT

CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8+ cytotoxic T lymphocytes. Engagement of CD160 by MHC class-I directly triggers a costimulatory signal to TCR-induced proliferation, cytokine production and cytotoxic effector functions. The role of CD160 in alloimmunity is unknown. Using a newly generated CD160 fusion protein (CD160Ig) we examined the role of the novel costimulatory molecule CD160 in mediating CD4+ or CD8+ T cell driven allograft rejection. CD160Ig inhibits alloreactive CD8+ T cell proliferation and IFN-γ production in vitro, in particular in the absence of CD28 costimulation. Consequently CD160Ig prolongs fully mismatched cardiac allograft survival in CD4−/−, CD28−/− knockout and CTLA4Ig treated WT recipients, but not in WT or CD8−/− knockout recipients. The prolonged cardiac allograft survival is associated with reduced alloreactive CD8+ T cell proliferation, effector/memory responses and alloreactive IFN-γ production. Thus, CD160 signaling is particularly important in CD28-independent effector/memory CD8+ alloreactive T cell activation in vivo and therefore may serve as a novel target for prevention of allograft rejection.

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