CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival
Ansari, Mohammed Javeed I.
MetadataShow full item record
CitationD’Addio, Francesca, Takuya Ueno, Michael Clarkson, Baogong Zhu, Andrea Vergani, Gordon J. Freeman, Mohamed H. Sayegh, Mohammed Javeed I. Ansari, Paolo Fiorina, and Antje Habicht. 2013. Cd160ig fusion protein targets a novel costimulatory pathway and prolongs allograft survival. PLoS ONE 8(4): e60391.
AbstractCD160 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11365693
- HMS Scholarly Articles