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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 18

PMID 23593209

Citations 14

Authors

Francesca DAddio

Takuya Ueno

Michael Clarkson

Baogong Zhu

Andrea Vergani

Gordon J Freeman

Mohamed H Sayegh

Mohammed Javeed I Ansari

Paolo Fiorina

Antje Habicht

Affiliations

Soon will be listed here.

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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