Differential function of intestinal intraepithelial lymphocyte subsets

It has been proposed that intestinal intraepithelial lymphocytes (I-IEL) perform immune surveillance of the epithelial layer (1) and regulate mucosal humoral responses to exogenous Ag (2). To better understand the functional potential of this unique population, purified murine I-IEL were analyzed phenotypically and functionally. Initial studies determined that I-IEL could be distinguished based on several phenotypic characteristics including: TCR (TCR-αβ vs TCR-γδ); Thy-1, CD45R/B220, CD5, and CD8 (CD8αα vs CD8αβ) expression. Using anti-TCR mAb, individual I-IEL subsets were activated and examined functionally. Both TCR-αβ and TCR-78 I-IEL were found to synthesize an array of lymphokines that included IL-2, IL-3, and IL-6 but not IL-4 or IL-5. Additionally, a number of lymphokines were detected that directly influence epithelial function (IFN-γ, TNF-α, and TGF-β1). However, the majority of the I-IEL function was localized within the Thy-1⁺, CD45R/B220^- I-IEL subset. In addition those TCR-αβ I-IEL expressing the CD8αβ heterodimer were more easily activated. Thus, a subset of I-IEL have the capacity to respond to TCR-mediated stimuli. The functional activities of these cells may influence both local immune cell populations as well as epithelial differentiation.