Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4+CD25+ T cells

Murine autoimmune gastritis, induced by neonatal thymectomy or the injection of CD25-depleted lymphocytes into nu/nu recipients, is characterized by an inflammatory infiltrate into the gastric mucose, parietal cell destruction and circulating anti-parietal cell antibodies. Using RAG-2(-/-) mice as recipients, we determined that the induction of disease relies on CD4(+)CD25(-) effector cells and prevention relies on CD4(+)CD25(+) regulatory cells; neither requires participation of CD8 cells or B cells. The severity of gastritis was dependent on the cytokine repertoire of CD4(+)CD25(-) effector T cells. Recipients of IL-4(-/-) T cells developed more severe gastritis and recipients of INF-gamma (-/-) T cells developed milder disease than recipients of wildtype or IL-10(-/-) effector T cells. Gastritis did not develop in the absence of IL-12. Protection from gastritis does not require either IL-4 or IL-10 because CD4(+)CD25(+) cells from IL-4(-/-) or IL-10(-/-) mice completely abrogated the disease process. CD4(+)CD25(+) cells also protected RAG-2(-/-) recipients from colitis and inhibitory activity was partially dependent on IL-10 expression. These findings highlight the critical role of CD4(+)CD25(+) regulatory T cells in protection from several autoimmune syndromes and delineate the differential contribution of IL-10 to CD4(+)CD25(+) Treg activity in the settings of gastritis and colitis. (C) 2001 Academic Press.