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Publication : Requirements for B7-CD28 costimulation in mucosal IgA responses: paradoxes observed in CTLA4-H gamma 1 transgenic mice.

First Author  Gärdby E Year  1998
Journal  J Immunol Volume  161
Issue  1 Pages  49-59
PubMed ID  9647206 Mgi Jnum  J:48172
Mgi Id  MGI:1266907 Doi  10.4049/jimmunol.161.1.49
Citation  Gardby E, et al. (1998) Requirements for B7-CD28 costimulation in mucosal IgA responses: paradoxes observed in CTLA4-H gamma 1 transgenic mice. J Immunol 161(1):49-59
abstractText  The block in the CD80/CD86-CD28/CTLA-4 pathway in CTLA4-H gamma 1 transgenic (Tg) mice results in strongly impaired systemic IgG immunity and failure to develop germinal center reactions. By contrast, here we report that mucosal immunity and IgA B cell differentiation are not affected by this block. We found abundant germinal centers and evidence of IgA switch differenti-ation in Peyer's patches, normal total IgA levels, and normal numbers of IgA-labeling cells in the gut mucosa. The distribution of B-1 and B-2 cells and the relative contribution of B-1 cells to the total IgA B cells were similar in Tg and wild-type mice. Despite this, oral immunizations with keyhole limpet hemocyanin plus cholera toxin adjuvant failed to stimulate Ag-specific mucosal IgA responses in CTLA4-H gamma 1 Tg mice. This was not due to a lack of adjuvant activity of cholera toxin in Tg mice, nor was this secondary to an inability to take up Ag from the gut lumen. Rather, CD4+ T cells stimulated by oral immunization in Tg mice appeared to be inappropriately primed, as evidenced by a significantly reduced level of CD40 ligand and CD44 expression and an increased expression of CD95 compared to those in wild-type mice. This study reveals a paradox in the regulation of mucosal IgA responses.
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