ICOS role in suppressing organ rejection

Chronic rejection, occurring a year or more following a transplant, remains a very common complication, despite continuous administration of immunosuppressants. But the mechanisms behind chronic rejection still remain obscure. In July Nature Immunology, Engin Özkaynak and colleagues from Millennium Pharmaceuticals in Boston show that a protein on T cells called inducible costimulator (ICOS) plays a key role in both acute and chronic rejection.

ICOS is a 55-60kD homodimer that is up-regulated after T cell activation and is particularly effective in costimulating IL-10 and IL-4. Using a murine transplant model, Özkaynak et al. found that both anti-ICOS antibody and an ICOS-Ig fusion protein suppressed intragraft T cell activation and cytokine expression, prolonging allograft survival in a manner similar to that in ICOS ^–/– allograft recipients. Two weeks of ICOS blockade and cyclosporin A treatment not only prevented acute rejection but also led to long-term acceptance of the transplant (Nat...