DENDRITIC EPIDERMAL T-CELLS INHIBIT T-CELL PROLIFERATION AND MAY INDUCE TOLERANCE BY CYTOTOXICITY

Hapten-conjugated cells of the dendritic epidermal T cell (DETC) line AU16 induce specific immunologic tolerance in vivo and inhibit the pro liferation of naive T cells in response to hapten-bearing dendritic ce lls in vitro. The purpose of this study was to test the hypothesis tha t these activities of DETC are mediated by a cytotoxic mechanism. In a ddition, because AU16 cells, unlike most DETC, express a TCR-alpha bet a, we compared their activity in the in vivo and in vitro assays with a TCR(+)-gamma delta DETC line (T245) and an TCR(+)-alpha beta, FITC-s pecific T cell line (T4/28). Hapten-conjugated AU16 and T245 cells, bu t not T4/28 cells, induced tolerance to FITC in vivo. In addition, the proliferative response of naive T lymphocytes to gamma-irradiated, ha pten-bearing APCs was inhibited by the addition of gamma-irradiated, F ITC-conjugated DETC to the cultures on day 0. To determine whether the T cell or the APC was the target, AU16 cells were added to the cultur es on day 4, when few APCs remained. FITC-conjugated AU16 and T245 cel ls profoundly inhibited [H-3]thymidine incorporation by the T cells, i ndicating that the T cell was the target of the DETC. Furthermore, AU1 6 cells reduced the number of T cells in the in vitro proliferation as say, suggesting that inhibition of [H-3]thymidine incorporation was a result of the cytotoxic activity of DETC. We speculate that cytotoxici ty may also account for the ability of DETC to induce tolerance in viv o.