This project is aimed at determining the molecular basis for CD4 T cell regulatory functions in the intestinal mucosa. We have previously shown that the majority to T cells in the intestinal lamina propria have the CD4+, Leu-8 - phenotype and that the Leu-8 molecule is the human lymph node homing receptor. A particular focus during the present period has been to determine the mechanisms by which CD4 T cell subpopulations mediate helper activity vs. inhibitory activity for B cell differentiation. Activated CD4+, Leu-8+ T cells had substantially lower levels of mRNA for IL-2, IL-4, IL-5 and IFN-gamma than CD4+, Leu-8- T cells. However, mRNA levels for actin, c-myc lL-2R and TGF-beta were similar in both subsets. Addition of IL-1, IL-2, IL-5, IL-6 or low molecular weight BCGF to pokeweed mitogen (PWM)-stimulated cultures did not reverse the low helper activity of CD4+, Leu-8+ T cells. Most importantly, in PWM-stimulated cultures containing B cells and CD4+, Leu-8- helper T cells, CD4+, Leu-8+ T cells suppressed Ig production when they were in direct contact with B cells. In contrast, there was little suppression when CD4+, Leu-8+ T cells were separated from B cells by a millipore membrane. Thus, the low helper activity of CD4+, Leu-8+ T cells may be due to an inherently lower capacity to produce B cell differentiation factors; their suppressor activity requires T-B contact and may be due to the release of novel inhibitory factors or a cytolytic mechanism. Future studies will determine the role of the Leu 8 molecule in contact dependent lymphocyte function and the mechanism of suppressor function of CD4+, Leu-8+ T cells.
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