Autologous mixed lymphocyte reaction in man. II. Histamine-induced suppression of the autologous mixed lymphocyte reaction by T-cell subsets defined with monoclonal antibodies

Abstract

Human peripheral blood mononuclear cells were separted into T and non-T cells by E-rosette formation. The influence of histamine (10−8−10−3 M) on the proliferative response of T cells in autologous and allogeneic mixed lymphocyte cultures (MLC) was studied. Pretreatment of responder T cells but not of stimulator non-T cells with histamine for 24 hr resulted in a markedly diminished proliferative response in both autologous and allogeneic MLC. A minimum of 4 hr of incubation of T cells with histamine was required to inhibit autologous MLC. Furthermore, T cells pretreated with histamine followed by mitomycin C treatment, when cocultured with fresh autologous T cells, suppressed their proliferative response in both autologous and allogeneic MLC. Analysis with OKT4 and OKT8 monoclonal antibodies revealed that histamine-induced suppressor T cells were contained in OKT 8 + -cell subset. Hitamine-treated OKT 4 + cells had no suppressive effect on the proliferative responses of autologous T cells. Supernatants of T cells cultured with histamine for 24 hr also suppressed both autologous and allogeneic MLC responses of fresh T cells, suggesting that the suppression could be mediated by a soluble suppressor factor(s). Experiments with H1 and H2 agonists and antagonists indicated that histamine-induced activation of suppressor T cells and the production of a soluble suppressor factor(s) were mediated through histamine type 2 receptors.