INDUCTION OF GUT MUCOSAL IMMUNE-RESPONSES - IMPORTANCE OF GENETIC BACKGROUND AND TH1 TH2 CROSS-REGULATION/

The reciprocal regulation of T-helper cell (Th) subsets is widely docu mented in various animal models of infectious diseases. In this study IFN-gamma/IL-4 double knockout (DKO) mice were used to analyse the rol e of Th subsets in mucosal immune responses. We found that the DKO mic e had normal IgA differentiation but impaired induction of specific gu t mucosal antibody responses after oral immunization using cholera tox in adjuvant. Both Th1 and Th2 responses were reduced compared with wil d-type mice. Despite the absence of both IFN-gamma and IL-4 in the DKO mice the overall results were similar to previous observations in IFN -gamma receptor-knockout (IFN-gamma R-/-) mice and did not suggest a s trict cross-regulation of the two Th subsets in the gut mucosa. To fur ther examine the role of IFN-gamma in mucosal immunity we compared two different mouse strains lacking IFN-gamma, i.e. IFN-gamma(-/-)(C57BL/ 6) and IFN-gamma R-/- mice (129/Sv). We found that IFN-gamma R-/- mice exhibited reduced mucosal antibody responses and decreased Th1 and Th 2 activity after oral immunization, while IFN-gamma(-/-) mice had inta ct antibody responses and increased Th2 responses. Thus, genetic diffe rences were found to critically affect the development of a specific g ut mucosal immune response. An enhanced Th2 activity in the Peyer's pa tches following oral immunization was associated with an ability to mo unt strong intestinal IgA immunity.