D’Addio, FrancescaUeno, TakuyaClarkson, MichaelZhu, BaogongVergani, AndreaFreeman, GordonSayegh, MohamedAnsari, Mohammed Javeed I.Fiorina, PaoloHabicht, Antje2013-12-102013D’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): e60391.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11365693CD160 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.en-USBiologyImmunologyImmune CellsT CellsImmunityImmune ActivationImmunologic SubspecialtiesTransplantationImmunologic TechniquesImmunoassaysAntigen Processing and RecognitionImmune ResponseMedicineClinical ImmunologyImmunotherapyMajor Histocompatibility ComplexJournal Article2013-12-1010.1371/journal.pone.0060391