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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

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.

N Okahashi, M Yamamoto, J L Vancott, S N Chatfield, M Roberts, H Bluethmann, T Hiroi, H Kiyono, J R McGhee
N Okahashi
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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M Yamamoto
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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J L Vancott
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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S N Chatfield
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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M Roberts
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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H Bluethmann
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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T Hiroi
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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H Kiyono
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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J R McGhee
Mucosal Immunization Research Group, University of Alabama, Birmingham Medical Center 35294, USA.
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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.

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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.
N Okahashi, M Yamamoto, J L Vancott, S N Chatfield, M Roberts, H Bluethmann, T Hiroi, H Kiyono, J R McGhee
Infection and Immunity May 1996, 64 (5) 1516-1525; DOI:

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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.
N Okahashi, M Yamamoto, J L Vancott, S N Chatfield, M Roberts, H Bluethmann, T Hiroi, H Kiyono, J R McGhee
Infection and Immunity May 1996, 64 (5) 1516-1525; DOI:
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