Heme oxygenase-1 modulates the allo-immune response by promoting activation-induced cell death of T cells

SPECIFIC AIMSHeme oxygenase-1 (HO-1), which degrades heme into three products (carbon monoxide, free iron, and biliverdin), plays a protective role in many models of disease via its anti-inflammatory, anti-apoptotic, and anti-proliferative actions. Expression of HO-1 suppresses immune responses and prolongs the survival of transplanted organs; however, the mechanism underlying these effects is not clear. We tested the hypothesis that HO-1 modulates the activation of T cells in a manner that helps sustain the survival of transplanted organs. We found that HO-1 exerts potent immunosuppressive effects in alloreactive T cells, preventing cells from mediating the rejection of transplanted organs.PRINCIPAL FINDINGS1. Induction of HO-1 expression by cobalt protoporphyrin IX (CoPPIX) inhibits alloantigen-driven T cell proliferationImportant as background information for the present study are our recent observations that HO-1 induction by cobalt protoporphyrin IX (CoPPIX) leads to significant prolongation of the s...