The role of adherent HLA-DR+ mononuclear cells in autologous and allogeneic MLR

Abstract

The aim of this study was to define the significance of HLA-DR+ cells for the in vitro induction of human autoreactive T cell proliferation. Proliferation was induced by autologous or allogeneic non-T cells or EB virus-transformed LCL. Pretreatment of stimulator cells with low concentrations of RAHLA-DR and C and with high amounts of RAHLA-DR alone abolished the capacity to stimulate autologous or allogeneic T cells. This suggested that antigens associated with HLA-DR+ stimulator cells or HLA-DR itself are involved in the induction of this proliferation. At the responder cell level the cytotoxic elimination of HLA-DR+ cells as well as depletion of adherent cells by passage through Sephadex G-10 columns reduced both autoreactive and alloreactive responsiveness. Responses of serologically and physically depleted populations were both restored by reconstitution with mitomycin-C treated autologous adherent cells. These cells were resistant to lysis with T cell specific antibodies and preferentially cooperated with T cells of autologous deprivation. Co-cultivation experiments further revealed that such accessory cells were capable of amplifying T cell proliferation in the presence of suboptimal numbers of autologous LCL. We concluded, therefore, that an HLA-DR+-adherent cell, presumably of monocytic origin, is required for optimal proliferative responsiveness of both autoreactive and alloreactive T cells.