Mucosal T-cell function

Lymphocytes in the intestinal lamina propria probably differ from lymphocyte populations in the circulation or in other tissue sites in a number of ways. First, lamina propria lymphocytes are phenotypically distinct in that few of these cells normally express the Leu-8 or CD45RA antigens. The presence of these molecules on CD4 T cells correlates with suppressor and suppressor-inducer function, and therefore the majority of CD4 T cells in the intestinal lamina propria have the phenotype associated with high helper activity. A substantial proportion of lamina propria lymphocytes also have evidence of activation, based on expression of the IL-2R alpha chain and HLA-DR molecules. Lymphocytes in the intestinal lamina propria are different in their potential for expression of lymphokine gene products, because activated cells from the lamina propria have high expression of mRNA for IL-2, IL-4, IL-5, and IFN-gamma in comparison to circulating lymphocytes. Mesenteric lymph node T cells also differ from circulating lymphocytes in their high expression of IL-4 and IL-5 mRNA. A further difference between mesenteric lymph node and lamina propria T cells is that the former can proliferate in response to IL-4, whereas the latter cannot. These phenotypic and mRNA differences of lamina propria lymphocytes also correlate well with their high helper activity in vitro for immunoglobulin synthesis in the pokeweed mitogen system. T cells with the potential for cytolytic activity are present in the intestinal lamina propria, although there is no definitive evidence that they are cytolytically active under physiologic or pathologic conditions. Finally, in a model system of intestinal inflammation, lymphogranuloma venereum in nonhuman primates, lamina propria T cells at the site of inflammation were unable to respond to specific antigens with proliferation but did respond with high helper activity. These observations are all consistent with the conclusion that T cells in the lamina propria are pleomorphic but are highly enriched for subpopulations of activated memory cells that are geared for effector functions such as helper and cytolytic functions. These functions are likely to be critical in maintaining normal host defense in the mucosal environment.