FUNCTION OF ALPHA-BETA-TCR(+) INTESTINAL INTRAEPITHELIAL LYMPHOCYTES - T(H)1-TYPE AND T(H)2-TYPE CYTOKINE PRODUCTION BY CD4(+)CD8(-) AND CD4(+)CD8(+) T-CELLS FOR HELPER ACTIVITY

The immunobiological function of lymphocytes within the epithelium (IELs) of the small intestine is incompletely understood; however, it has been shown that intestinal IEL T cells exhibit cytotoxicity, produce cytokines, and perform some regulatory roles. In this study, we have focused on CD4+, alphabeta TCR+ IELs, which comprise approximately 15 - 20% of the total population, for helper functions. We have assessed the profile of type 1 or type 2 Th cell cytokines produced in alphabeta TCR bearing CD4+CD8- and CD4+CD8+ (double positive, DP) intestinal IELs by cytokine-specific ELISPOT and by reverse transcription-polymerase chain reaction. Help for B cells taken from Peyer's patches (PP) allowed us to assess IEL function for mucosal antibody responses. Freshly isolated CD4+CD8- IEL T cells contain T(h)2-type cells, e.g. high numbers of IL-5 secreting (spot forming) cells (SFC) followed by IL-4 and IL-6, while DP T cells have IL-5 and IL-6 producing cells, but not IL-4. In addition to T(h)2-like cytokine producing T cells, both CD4+ T cell subsets contain IFN-gamma secreting T(h)1-type cells but neither subset synthesizes IL-2. Stimulation of CD4+CD8- and DP T cells with solid phase mAb anti-CD3 resulted in production of IL-2 in addition to IFN-gamma, IL-5, and IL-6, and this treatment stimulated DP T cells to produce IL-4. When freshly isolated intestinal IEL T cells were separated into CD4+ and CD4- cells, and co-cultured with PP B cells, the former subset supported Ig synthesis including IgA responses, while the later fraction did not. Further, purified alphabeta TCR+, CD4+CD8- T cells and DP T cells from IELs when added to PP B cell cultures induced increased numbers of Ig secreting cells. However, CD4-CD8+ T cells which produced a similar profile of cytokines did not provide helper function for B cells. Our study has shown that alphabeta TCR+ T cells from intestinal IELs exhibit T(h)1- and T(h)2-type cell functions. Of significant interest was the finding that DP T cells exhibit cytokine synthesis and helper function in the epithelium of the gastrointestinal tract in addition to CD3+ IELs expressing a classical helper phenotype (CD4+CD8-).