The data show that although Treg from Gαi2−/− mice are functional in vitro, and are present at enhanced frequency within the CD4+ infiltrate in colitis, they are unable to prevent disease caused by endogenously activated Gαi2−/− effector T cells, the latter being significantly more resistant to suppression by either wild type or Gαi2−/− Treg. The gene discussed is CD4; the disease is colitis.