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Induction of Gut Mucosal Immune Responses: Importance of Genetic Background and Th1/Th2 Cross‐Regulation
Author(s) -
Martin Kjerrulf,
Dubravka Grdic,
Manfred Köpf,
Nils Lycke
Publication year - 1998
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1998.00316.x
Subject(s) - immune system , immunology , biology , cholera toxin , antibody , immunization , immunity , knockout mouse , adjuvant , receptor , mucosal immunity , microbiology and biotechnology , genetics
The reciprocal regulation of T‐helper cell (Th) subsets is widely documented in various animal models of infectious diseases. In this study IFN‐γ/IL‐4 double knockout (DKO) mice were used to analyse the role of Th subsets in mucosal immune responses. We found that the DKO mice had normal IgA differentiation but impaired induction of specific gut mucosal antibody responses after oral immunization using cholera toxin adjuvant. Both Th1 and Th2 responses were reduced compared with wild‐type mice. Despite the absence of both IFN‐γ and IL‐4 in the DKO mice the overall results were similar to previous observations in IFN‐γ receptor‐knockout (IFN‐γR −/− ) mice and did not suggest a strict cross‐regulation of the two Th subsets in the gut mucosa. To further examine the role of IFN‐γ in mucosal immunity we compared two different mouse strains lacking IFN‐γ, i.e. IFN‐γ −/− (C57BL/6) and IFN‐γR −/− mice (129/Sv). We found that IFN‐γR −/− mice exhibited reduced mucosal antibody responses and decreased Th1 and Th2 activity after oral immunization, while IFN‐γ −/− mice had intact antibody responses and increased Th2 responses. Thus, genetic differences were found to critically affect the development of a specific gut mucosal immune response. An enhanced Th2 activity in the Peyer's patches following oral immunization was associated with an ability to mount strong intestinal IgA immunity.