Localization of IFN-gamma and IL-6 mRNA in murine intestine by in situ hybridization.

Previous studies have highlighted the importance of CD4+ T cells in regulation of IgA responses and have indicated a functional heterogeneity among these cells between inductive (Peyer's patch) and effector (lamina propria) sites in the intestine. To determine whether these functional differences could be accounted for by differences in cytokine profile of cells in each of these sites, the distribution of mRNA for interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) was investigated by in situ hybridization techniques using 35S-labelled riboprobes. Whereas message for IL-6 is abundant in all regions of the lamina propria from the base of the mucosa to the tips of the villi, very little is expressed in Peyer's patches or in the epithelium. In contrast, message for IFN-gamma is expressed predominantly by cells localized only in the base of the lamina propria and, as with IL-6, very little message was detected in Peyer's patches although occasional strongly positive IFN-gamma cells were observed in the epithelium. These results indicate that, at least in the absence of deliberate intestinal stimulation, functional expression of these cytokines is restricted to effector rather than induction sites in the intestine. This is consistent with our previous observations demonstrating a requirement for T-cell signals in promoting post-extravasation differentiation and proliferation of IgA-committed B cells in vivo and the implications of these findings to the role of the Th1 and Th2 subsets of CD4+ cells in mucosal immune responses is discussed.