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 documented in various animal models of infectious diseases. In this study IFN-gamma/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-gamma and IL-4 in the DKO mice the overall results were similar to previous observations in IFN-gamma receptor-knockout (IFN-gammaR-/-) 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-gamma in mucosal immunity we compared two different mouse strains lacking IFN-gamma, i.e. IFN-gamma-/- (C57BL/6) and IFN-gammaR-/- mice (129/Sv). We found that IFN-gammaR-/- mice exhibited reduced mucosal antibody responses and decreased Th1 and Th2 activity after oral immunization, while IFN-gamma-/- 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Animals

Antibody Formation

Female

Immunity

Mucosal

genetics

immunology

Immunoglobulin A

Secretory

immunology

Interferon-gamma

genetics

Interleukin-4

genetics

Intestinal Mucosa

immunology

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Peyer's Patches

immunology

Proteins

immunology

Receptors

Interferon

genetics

Solubility

Th1 Cells

immunology

Th2 Cells

immunology

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