CHEMOKINE EXPRESSION BY INTRAEPITHELIAL GAMMA-DELTA T-CELLS - IMPLICATIONS FOR THE RECRUITMENT OF INFLAMMATORY CELLS TO DAMAGED EPITHELIA

T cells expressing gamma delta TCR may have evolved to recognize Ag in a different manner as well as perform a broader set of functions than T cells with alpha beta TCR. In this study, we tested the hypothesis that dendritic epidermal T cells (DETC) bearing the invariant V gamma 3V delta 1 TCR may be able to signal the migration of peripheral alpha beta T cells to the epidermis by secreting specific chemokines. Expre ssion of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RA NTES, and lymphotactin was inducible in DETC 7-17 cells, whereas mRNA for monocyte chemoattractant protein (MCP)-1 could not be detected. St rikingly, lymphotactin was the most abundant chemokine produced by act ivated 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 gamma delta TCR expressed high levels of lymphotactin mRNA, In contrast, lymphotac tin mRNA was present in activated spleen gamma delta T cells at low ba sal 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 b y neutralizing anti-MIP-1 alpha, anti-MIP-1 beta, or anti-RANTES antis erum. The presence of lymphotactin in supernatants from activated DETC 7-17 cultures was directly demonstrated by Western blot analysis, The se observations are consistent with a model in which gamma delta IEL p lay an active multifaceted role in the maintenance of epithelia homeos tasis.