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Paradoxical IgA immunity in CD4-deficient mice. Lack of cholera toxin-specific protective immunity despite normal gut mucosal IgA differentiation.

C E Hörnquist, L Ekman, K D Grdic, K Schön and N Y Lycke
J Immunol September 15, 1995, 155 (6) 2877-2887;
C E Hörnquist
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L Ekman
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K D Grdic
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K Schön
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N Y Lycke
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Abstract

Using normal and CD4 gene-targeted (CD4-/-) mice, we asked whether mucosal immune responses and IgA B cell differentiation require the presence of CD4+ T helper cells. We found that CD4-/- mice had numerous B cell germinal centers in Peyer's patches and other gut-associated lymphoid tissues. Membrane IgA+ B cells were found to co-localize to germinal center areas and CD4-CD8- double negative CD3+ T cells had replaced CD4+ T cells in the follicular areas of the Peyer's patches. CD4-/- mice had normal levels of IgA-producing cells in gut-associated lymphoid tissues, and gut lavage contained unaltered levels of total IgA. However, despite T cell help for IgA B cell differentiation, CD4-/- mice did not respond with Ag-specific intestinal IgA following oral immunization with the powerful mucosal immunogen cholera toxin (CT). By contrast, these mice demonstrated serum alpha-CT IgG following oral immunization, suggesting that double negative CD3+ T cells provided some help for systemic immune responses after oral immunization. Perorally immunized CD4-/- mice were completely unprotected against CT-induced diarrhea while both normal and CD8-/- mice were well protected and also demonstrated high levels of gut mucosal alpha-CT IgA. After reconstitution of the CD4-/- mice by adoptive transfer of naive mesenteric lymph node CD4+ T cells, the mice acquired the ability to respond with specific mucosal immune responses following oral immunization and also developed resistance against CT-induced diarrhea. Thus, paradoxically, although IgA B cell differentiation appears to proceed normally in CD4-/- mice, specific gut mucosal immune responses are grossly impaired in the absence of CD4+ T cells.

  • Copyright © 1995 by American Association of Immunologists
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The Journal of Immunology
Vol. 155, Issue 6
15 Sep 1995
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Paradoxical IgA immunity in CD4-deficient mice. Lack of cholera toxin-specific protective immunity despite normal gut mucosal IgA differentiation.
C E Hörnquist, L Ekman, K D Grdic, K Schön, N Y Lycke
The Journal of Immunology September 15, 1995, 155 (6) 2877-2887;

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Paradoxical IgA immunity in CD4-deficient mice. Lack of cholera toxin-specific protective immunity despite normal gut mucosal IgA differentiation.
C E Hörnquist, L Ekman, K D Grdic, K Schön, N Y Lycke
The Journal of Immunology September 15, 1995, 155 (6) 2877-2887;
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