Induction of T helper cells and cytokines for mucosal IgA responses

Abstract

CD4+ Th cells and their derived cytokines play an important role in the regulation of IgA responses in the mucosal immune system. Th1 and Th2 cells induce different Ig isotype and IgG-subclass responses. Further, cytokines produced by Th2-type cells (e.g., IL-5 and IL-6) have been shown to induce PP sIgA+ B cells to secrete IgA. Our studies have now shown that oral immunization with SRBC selectively induces Th2-type cells in PP while systemic (I.P.) immunization with SRBC predominantly induces Th1-type cells. It is tempting to suggest that Th2 cells which produce IL-5 and IL-6 tend to be predominant in mucosal effector regions, such as the salivary glands and LP tissues and account for the predominant IgA responses which characterize these tissues. The PP contain B cell subsets which respond to IL-5 and IL-6, and these are largely restricted to the PNALo non-GC (memory) sIgA+ B cells. The importance of CD4+ Th cells in the regulation of IgA responses has also been shown by the depletion of CD4+ Th cells in anti-L3T4 (CD4)-treated mice. Loss of CD4+ Th cells from mucosal tissues resulted in dramatically decreased numbers of IgA plasma cells in the small intestine and led to a reduction in IgA SFC in isolated LP cells. The overall size of PP was reduced and the GCs were absent; however, the relative frequency of sIgA+ B cells in PP did not change, possibly suggesting that CD4+ Th cells do not influence switches to IgA.