Activation of phenotypically heterogeneous murine T cell receptor gamma delta + dendritic epidermal T cells by self-antigen(s).

Adult murine epidermis contains a population of Thy-1+, CD45+, CD3+, CD4- and CD8- in situ primarily T cell receptor (TCR) V gamma 3+/V delta 1+ dendritic epidermal T cells (DETC). In the present study, cell surface phenotypes as well as functional properties of DETC were characterized by using in vitro mitogen-stimulated short-term- (10 days) and cloned long-term-cultured (> 1 year) DETC lines. Phenotypic characterization revealed that > 80% of the short-term-cultured cells were routinely TCR gamma delta +, CD4-, CD8-. The majority expressed the V gamma 3 TCR. Seventy-five percent of the lines contained detectable numbers of V gamma 2+ (5-7%) and V gamma 2-3- cells (2-3%). Four different types of stable TCR gamma delta +, CD4-, CD8- long-term-cultured clones were found: TCR V gamma 3+, V gamma 2+, V gamma 2-3- and V gamma 2-3-MHC-class-II+ clones. Nine of the 15 DETC clones tested were activated to proliferate in the presence of dendritic cells or macrophages, while keratinocytes were not stimulatory. This reactivity of DETC was mediated by the TCR and was apparently not MHC-restricted. Only the V gamma 3+, V gamma 2-3- or V gamma 2-3-MHC-class-II+DETC clones were self-responsive. Short-term-cultured DETC clones were self-responsive. Short-term-cultured DETC lines also exhibited the same reactivity. There was no specific cytokine profile of self-reactive DETC. Upon mitogen stimulation, short-term-cultured DETC lines secreted interleukin (IL)-2, IL-3, IL-4 and interferon (IFN)-gamma. In contrast, none of the long-term-cultured DETC clones produced IL-4. Four different profiles were discernible for the other lymphokines tested, irrespective of the clones' phenotype and reactivity towards accessory cells. The manifested profiles were IL-2, IL-3 and IFN-gamma, IL-2 and IL-3, IFN-gamma only and none of the tested lymphokines. The results suggest that DETC may comprise functionally different subsets and support the notion that DETC may exhibit immunorelevant activities in conjunction with natural neighboring cells.