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ABSTRACT: 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 exhibitcytotoxiclty, produce cytokines, and perform some regulatory roles. In this study, we have focused on CD4+, αβ TCR+ IELs, which comprise∼15—20%; of the total population, for helper functions. We have assessed the profile of type 1 or type 2 T h cell cytokines produced in αβ 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-γ, 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-γ, 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 αβ 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 αβ 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−).