Conclusions
Mucosal immune responses are strongly regulated by CD4+ T cells and their derived cytokines. In this regard, IFN-γ−/− mice (i.e., which lack Th1 and have elevated Th2 cells) showed strong mucosal Th2-type responses together with S-IgA production, while IL-4−/− (e.g., dominant Th1 and lack of Th2 cells) mice had impaired mucosal Th2 and IgA responses following oral delivery of TT and CT. However, when rSalmonella or radenovirus were used for antigen delivery, significant levels of mucosal IgA responses were induced in both IFN-γ−/− and IL-4−/− mice. The choice of the antigen delivery system which leads to optimal Th and B cell interactions are important for the induction of effective IgA responses, even in situations where the immune system is compromised. It is clear that Th2-type cytokines are important in mucosal IgA responses; however, other cytokine combinations can compensate for mucosal immunity in situations in which Th2 cell responses are absent. Mucosally induced tolerance may be one approach to prevent several systemic immune disorders; however, the mechanism of this phenomenon still needs to be elucidated. Our recent findings have suggested that IFN-γ may play an important role in induction of systemic unresponsiveness since oral tolerance was not induced in IFN-γ−/− mice.
Our studies as well as those of others indicated that at least two phases of a triad of cell interactions are important for the mucosal immune system. First, it has been shown that epithelial cell-produced IL-7 and SCF andαβ T cell-derived IL-2 are essential activation and growth signals for intestinalγδ T cells. Second, our studies with TCRδ knockout mice have suggested that mucosalγδ T cells also play a critical role in the regulation of mucosal IgA responses. Thus, a mucosal internet amongγδ T cells,αβ T cells, and IgA B cells appear critical for mucosal homeostasis and for regulation of specific mucosal immune responses.
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Fujihashi, K., Kweon, MN., Kiyono, H. et al. A T cell/B cell/epithelial cell internet for mucosal inflammation and immunity. Springer Semin Immunopathol 18, 477–494 (1997). https://doi.org/10.1007/BF00824054
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DOI: https://doi.org/10.1007/BF00824054