BLOCKING THE CD28-B7 T-CELL COSTIMULATION PATHWAY INDUCES LONG-TERM CARDIAC ALLOGRAFT ACCEPTANCE IN THE ABSENCE OF IL-4

Blocking the CD28-B7 T lymphocyte costimulatory pathway with the recom binant protein CTLA4lg induces long term allograft survival in rodents . It has been suggested that this results from selective activation of the Th2 immune pathway. To test this hypothesis, we compared vascular ized cardiac allograft survival in wild-type (IL-4 +/+) and homozygous IL-4 gene-knockout (IL-4 -/-) mice. We report in this study that long term survival (>100 days) of fully allogeneic grafts can be induced r eadily in IL-4 -/- recipients treated with a short course of CTLA4lg. We also demonstrate that IL-4 -/- mice are deficient in Th2-type cytok ine expression following in vitro or in vivo allostimulation. These re sults suggest that IL-4 production and subsequent generation of a Th2- type immune response are not obligatory for CTLA4lg-induced long term acceptance of vascularized allografts.