Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses. Infection and immunity. [Infect Immun] Journal article | | Title | Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses. | | Author(s) | Okahashi N, Yamamoto M, Vancott JL, Chatfield SN, Roberts M, Bluethmann H, Hiroi T, Kiyono H, McGhee JR | | Institution | Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA. | | Source | Infect Immun 1996 May; 64(5):1516-25. | | MeSH | Adjuvants, Immunologic
Administration, Oral
Animals
Antigens, Bacterial
Cholera Toxin
Cytokines
Immunization
Immunoglobulin A
Immunoglobulin E
Immunoglobulin G
Interleukin-10
Interleukin-4
Interleukin-6
Mice
Mice, Inbred C57BL
Mice, Knockout
Mucous Membrane
RNA, Messenger
Rats
Rats, Inbred F344
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Salmonella
Tetanus Toxin
Th2 Cells
| | Abstract | Mucosal immunoglobulin A (IgA) responses are often associated with Th2-type cells and derived cytokines, and interleukin-4 (IL-4) knockout (IL-4-/-) mice with impaired Th2 cells respond poorly to oral antigens. However, we have noted that IL-4-/- mice have normal mucosal IgA levels, which led us to query whether different oral delivery systems could elicit mucosal immunity. Two oral regimens were used: (i) a live recombinant Salmonella strain which expresses fragment C (ToxC) of tetanus toxin, and (ii) soluble tetanus toxoid (TT) with cholera toxin (CT) as an adjuvant. Oral immunization of IL-4-/- mice with recombinant Salmonella vaccine expressing ToxC induced brisk mucosal IgA and serum IgG (mainly IgG2a) anti-TT antibody responses. TT-specific CD4+ T cells from spleen or Peyer's patches produced gamma interferon, indicative of Th1 responses; however, IL-6 and IL-10 were also seen. Oral immunization of IL-4-/- mice with TT and CT induced weak mucosal IgA to TT; however, brisk IgA anti-CT-B responses and CT-B-specific CD4+ T cells producing IL-6 and IL-10 were also noted. These results show that although IL-4-dependent antibody responses are impaired, mucosal IgA responses are induced in IL-4-/- mice. These result suggest that certain cytokines, i.e., IL-6 and IL-10 from Th2-type cells, play an important compensatory role in the induction and regulation of mucosal IgA responses. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 8613355 |
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