Owing to the observation that CD8+ T cells in CD28 agonist-treated immunologically experienced septic mice exhibited increased IL-10 secretion and our published finding that IL-10 neutralization erases the benefit of CD28 agonism in immunologically experienced septic mice (10), we conclude that the immunoregulatory effect of IL-10-producing CD8+ Foxp3+ T cells contributes to the salutary effect of CD28 agonism during sepsis in immunologically experienced hosts. The gene discussed is CD8A; the disease is Sepsis.