Role of gamma delta T cells in the regulation of mucosal IgA response and oral tolerance

In this short review, we first described experiments that show that prolonged oral immunization with a protein vaccine, such as DT, induces systemic unresponsiveness in the presence of antigen-specific mucosal IgA responses. Mucosal T cells, such as IEL, may play an important role for the maintenance of antigen-specific IgA responses because these T cells are able to respond to stimulation signals provided by antigen even when T-cell unresponsiveness was induced in systemic tissue, such as spleen of mice orally tolerized with the protein DT. Inasmuch as IEL contain a high frequency of γδ T cells, it was logical to postulate that mucosal γδ T cells are essential regulatory T cells for the induction of IgA responses in oral tolerance. To this end, our previous studies showed that adoptive transfer of mucosal γδ T cells from IEL of mice orally tolerized with SRBC to the recipient mice with systemic unresponsiveness to the same antigen resulted in the abrogation of unresponsiveness to Ig synthesis, including those of IgA isotype. In this regard, when the mucosal immune system of TCR-δ(-/-) and their control mice was examined, lower numbers of IgA antibody-producing cells were noted in TCR-δ(-/-) mice in comparison to control background mice. Further, the level of IgA in fecal extracts was also low in TCR-δ(-/-) mice. These findings suggested that loss of γδ T cells results in down-regulation of IgA B-cell responses.