Proliferative properties of murine intestinal intraepithelial lymphocytes (IEL): IEL expressing TCRαβ or TCRτδ are largely unresponsive to proliferative signals mediated via conventional stimulation of the CD3-TCR complex

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Abstract
Murine intestinal intraepithelial lymphocytes (IEL) were studied for their capacity to proliferate in vitro following stimulation of the T cell receptor (TCR)-associated CD3ε molecule, or upon direct stimulation of the TCR complex itself. Although IEL consisted primarily of CD3+ T cells which included activated cytotoxicT lymphocytes as demonstrated in CD3- and TCR-mediated redirected cytotoxic assays, IEL displayed minimal proliferative responses following stimulation with anti-CD3, anti-TCRαβ or antl-TCRτδ monocional antibodies under soluble conditions, or under conditions which effect membrane cross-linking, including the addition of accessory cells toIEL cultures. The lack of proliferation induction could not be overcome by stimulation of IEL In the presence of T cell-dependent cytokines, phorbol ester, or interieukin-4. Moreover, unlike splenic T cells, stimulation of IEL failed to result In expression of interleukln-2 receptor, further demonstrating an Inability of IEL to respond to exogenous proliferatlve signals. This study Is the first to examine the proliferative potential of murine IEL following direct CD3 or TCR stimulation. The findings described here: (i) identify an important functional distinction between intestinal IEL and other peripheral αβ or τδ T cells which generally respond well to proliferative signals mediated through the CD3-TCR complex, and (ll) demonstrate that on murine IEL the CD3-TCR complex can discriminate signals of lytlc activityfrom those of cell proliferation.

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