Analysis of the mucosal microenvironment: factors determining successful responses to mucosal vaccines

The predominance of IgA antibodies in mucosal sites reflects a combination of high rate IgA isotype switching among precursor cells in induction sites , their selective localisation in mucosal effector tissues and vigorous pro liferation of these cells after extravasation. Each of these steps leading to IgA expression at the mucosa is under cytokine control. This paper will address the role of cytokines in induction and expression of IgA responses, the contribution of various precursor cell subsets and their differential responses to cytokine signals and strategies for manipulating cytokine expr ession. With respect to IgA antibody production in the gut whereas IL-4 and TGF-bet a have been implicated in isotype switching of precursor cells to IgA commi tment, their subsequent localisation, proliferation and effector activity e xpression is dependent on IL-5 and IL-6 expression locally. Most IgA plasma cells in the intestine derive from cells of the B2 lineage in the Peyer's patch, but a subpopulation of cells derived from the peritoneal cavity (B1 cells) also contribute to the IgA plasma cell population in the intestinal lamina propria. Whereas IgA(+) cells of the B2 Lineage are IL-6 dependent b ut IL-5 independent, BI-derived IgA(+) cells are IL-5 dependent and IL-6 in dependent. On the other hand, cell mediated immune responses in the gut are highly dependent on IFN-gamma production by both Th1 CD4 cells and CD8 cel ls and in enteric Salmonella infection IFN-gamma production is essential bu t antibody has little effect on this process. Therapeutic interventions based on the information emerging from these stud ies will lead to improved vaccination responses and correction of immunodef iciencies especially in young animals. (C) 1999 Elsevier Science B.V. All r ights reserved.