| First Author | Hörnquist CE | Year | 1995 |
| Journal | J Immunol | Volume | 155 |
| Issue | 6 | Pages | 2877-87 |
| PubMed ID | 7673704 | Mgi Jnum | J:110845 |
| Mgi Id | MGI:3641387 | Doi | 10.4049/jimmunol.155.6.2877 |
| Citation | Hornquist CE, et al. (1995) Paradoxical IgA immunity in CD4-deficient mice. Lack of cholera toxin-specific protective immunity despite normal gut mucosal IgA differentiation. J Immunol 155(6):2877-87 |
| abstractText | 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. |