Impaired B cell responses to orally administered antigens in lamina propria but not Peyer's patches of Gαi2-deficient mice prior to colitis

Abstract

Despite numerous studies on the intestinal immune system in patients with inflammatory bowel disease (IBD) and animal models of IBD, very little is known about the immune reactivity of mucosal lymphocytes following oral immunizations under these circumstances. The reactivity of Peyer's patch (PP) and lamina propria (LP) T and B lymphocytes in inhibitory G-protein α2 subunit-deficient (Gαi2-/-) mice developing an IBD resembling ulcerative colitis was investigated following repeated oral immunizations with keyhole limpet haemocyanin (KLH), together with the adjuvant cholera toxin, prior to colitis. The antigen-specific B-cell response in the LP of both the small and the large intestines was significantly reduced in Gαi2 -/- as compared to wild-type mice. In contrast, the frequency of KLH-specific immunoglobulin (Ig)-producing cells in the PP did not differ between Gαi2-/- and wild-type mice, whereas the total frequency of Ig-producing cells as well as the frequency of enteric flora-specific Ig-producing cells in the PP was significantly increased in Gαi2 -/- as compared to wild-type mice. Analysis of T cell responses following restimulation ex vivo with KLH revealed a dramatic increase in the production of interferon-γ in mesenteric lymph node, PP and LP lymphocytes from Gαi2-deficient as compared to wild-type mice, together with decreased production of interleukin-10 in all locations except the PP. © 2005 Blackwell Publishing Ltd.