Chemokine expression by intraepithelial γ δ T cells. Implications for the recruitment of inflammatory cells to damaged epithelia

Abstract

T cells expressing γ δ TCR may have evolved to recognize Ag in a different manner as well as perform a broader set of functions than T cells with α β TCR. In this study, we tested the hypothesis that dendritic epidermal T cells (DETC) bearing the invariant V γ 3V δ 1 TCR may be able to signal the migration of peripheral α β T cells to the epidermis by secreting specific chemokines. Expression of macrophage inflammatory protein (MIP)-1 α, MIP-1 β, RANTES, and lymphotactin was inducible in DETC 7-17 cells, whereas mRNA for monocyte chemoattractant protein (MCP)-1 could not be detected. Strikingly, lymphotactin was the most abundant chemokine produced by activated DETC 7-17 cells. Activated primary DETC cultures also produced copious amounts of lymphotactin mRNA. Similarly, freshly isolated and activated intestinal intraepithelial T cells (i-IEL) with γ δ TCR expressed high levels of lymphotactin mRNA. In contrast, lymphotactin mRNA was present in activated spleen γ δ T cells at low basal levels. Migration of CD8+ T cells induced by culture supernatants from stimulated DETC 7-17 cells was strongly reduced in the presence of a neutralizing anti-lymphotactin antiserum and to a lesser extent by neutralizing anti-MIP-1 α, anti-MIP-1 β, or anti-RANTES antiserum. The presence of lymphotactin in supernatants from activated DETC 7-17 cultures was directly demonstrated by Western blot analysis. These observations are consistent with a model in which γ δ IEL play an active multi-faceted role in the maintenance of epithelia homeostasis.