CD160Ig fusion protein targets a novel costimulatory pathway and prolongs allograft survival.

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.