Epidermal cell-induced generation of cytotoxic T-lymphocyte responses against alloantigens or TNP-modified syngeneic cells: requirement for Ia-positive Langerhans cells

Abstract

The role of epidermal cells (EC) in the activation of T-cell proliferation is well established. In this study we asked whether EC can provide a stimulus resulting in the generation of genetically restricted T-cell cytotoxicity. For this purpose, C57Bl/6 or C3H/He highly purified, accessory cell-depleted responder splenic T lymphocytes, were stimulated in 5-day cell-mediated cytotoxicity cultures with mitomycin C-treated allogeneic or trinitrophenyl (TNP)-modified syngeneic EC, or, for control purposes, with unfractionated spleen cells (SC). Untreated and complement (C')-treated EC induced strong cytotoxic T lymphocyte (CTL) activity in highly purified allogeneic T cells and, in analogy, TNP-modified EC led to the generation of TNP-self CTL, as tested in 4-h 51Cr release assays against allogeneic or TNP-modified syngeneic EC or SC targets. These cytotoxic responses were comparable in magnitude to those seen with allogeneic or TNP-modified syngeneic SC stimulators. In contrast, alloreactive or TNP-self CTL responses were not generated when stimulating EC were depleted of Langerhans cells by pretreatment with anti-Ia monoclonal antibodies plus C' or, for control purposes, when highly purified T-cell stimulators were used. These results demonstrate that EC induce the generation of alloreactive and TNP-self CTL in the absence of Ia-positive splenic accessory cells and that Ia-bearing Langerhans cell are required for this process to occur.