Interleukin (IL)-15 Promotes the Growth of Murine Epidermal γδ T Cells by a Mechanism Involving the β- and γc-Chains of the IL-2 Receptor

Abstract

Dendritic epidermal T cells (DETC) are skin-specific members of the epithelial gamma delta T-cell family in mice. We have reported previously that the growth of DETC is promoted by interleukin (IL)-2 in an autocrine fashion, or by IL-7, which is secreted by neighboring keratinocytes. Here we report that DETC growth is promoted by IL-15, a newly discovered T-cell growth factor that is produced in lymphoid as well as nonlymphoid tissues. Recombinant IL-15 promoted the growth of the 7-17 DETC line in a time- and dose-dependent fashion. Using monoclonal antibodies against alpha-, beta-, or gamma c-chains of the IL-2 receptor complex, we observed that the combination of anti-beta chain and anti-gamma c chain antibodies blocked IL-15 responsiveness completely, whereas anti-alpha chain had no effect. These results indicate that this gamma delta T-cell line uses the beta/gamma c heterodimer for proliferative responses to IL-15. Antibodies against IL-2 or IL-7 did not block IL-15-driven proliferation of 7-17 DETC, indicating that IL-15 promotes their growth in an IL-2- and IL-7-independent manner. Both the surface expression of beta/gamma c heterodimers and the IL-15 responsiveness of 7-17 DETC were highest 1 to 8 days after concanavalin A stimulation, and both declined substantially 21 days after stimulation, illustrating regulation by the state of cell activation. Working with epidermal cells that were freshly procured from CBA mice, we noted that IL-15 promoted conavalin-A-triggered growth of Thy-1+ cells (i.e., DETC), but not of the Thy-1- cells. The gamma c-chain was not expressed by freshly procured DETC, becoming detectable within 48 h after concanavalin A stimulation. We propose that IL-15 facilitates the growth of epithelial gamma delta T cells by a beta/gamma c receptor-dependent mechanism.