Regulation of mucosal immune responses by T lymphocytes: the effect of chronic CD4+ T cell deficiency on IgA synthesis.

Mechanisms of immune defence at the mucosal surface has been elucidated by recent advances in molecular and cellular immunology. IgA is undoubtedly the most important defense factor in the mucosal immune system. It has been shown that T cells are essential for the induction and regulation of IgA synthesis. In T cell regulation of IgA synthesis, various cytokines (e.g., TGF-beta, IL-2, IL-5, and IL-6) which are secreted by CD4+ T cells, play important roles for the induction and regulation of IgA isotype switching and terminal differentiation of sIgA+ B cells to become IgA producing cells. The chronic treatment of mice with anti-CD4 mAb induced a market deficiency of CD4+ T cells in both mucosal and systemic tissues. IgA plasma cells were significantly reduced in treated mice when compared with normal mice (greater than 80% reduction), while the numbers of sIgA+ B cells in IgA inductive sites (e.g., PP) remained normal. CD4+ Th cells are a critical element for the induction of appropriate IgA responses in mucosal associated tissues. Elucidation of the precise cellular and molecular network for the regulation of mucosal immune defense system is important and useful for the consideration of prevention of infectious diseases. In this regard, the effective and sophisticated mucosal administration of vaccines using the concept of the common mucosal immune system should induce effective immune responses which prevent the pathogen from entering the host through large surface areas of mucosal membranes. This goal cannot be achieved without a more complete understanding of regulatory T cells and cytokines for mucosal immune responses.