Cellular interactions in the generation and expression of histamine-induced suppressor activity

Abstract

Employing a coculture assay and techniques for fractionation of human peripheral blood mononuclear cells (PBMC), we have analyzed the cellular interactions required for the generation and expression of histamine-induced suppressor activity. PBMC cultured in the presence of histamine (10 −4 to 10 −3 M) for 24 hr could function as suppressor cells. In order to determine the role played by monocytes in the generation phase of suppressor cell activation, PBMC were fractionated over nylon wool columns and depleted of adherent cells. The nylon wool nonadherent T (NWNA-T) cells were unable to be activated to express suppressor activity. However, suppressor cell function by NWNA-T cells was reconstituted by the readdition of autologous monocytes in the form of glass adherent cells. In addition, the requirement for intact monocytes to be present during the activation process could be bypassed by culturing the NWNA-T suppressor population in supernatants derived from mononuclear phagocytes stimulated by phagocytosis of heat-killed Staphylococcus albus. The role of monocytes in the effector phase of suppression was analyzed using NWNA-T populations cultured in the presence of monocyte supernatant factors for both the generation and effector phases of the coculture assay. Depletion of monocytes from both the suppressor and indicator populations resulted in a marked reduction in the expression of histamine suppressor activity despite the presence of monocyte supernatant factors. The addition of indomethacin at the time of co-culture (effector phase) abrogated histamine-induced suppression when monocytes were present in the indicator population. In contrast, indomethacin had no effect on the activation of suppressor cells. In related experiments, supernatants containing histamine-induced suppressor factor activity increased the production of PGE by human blood monocytes. Taken together, these results indicate that monocytes and/or monocyte factors perform a vital accessory function in the generation of histamine-induced suppressor T cells as well as during their subsequent modulation of lymphoproliferation. Furthermore, the monocyte factors involved in each phase (afferent and efferent) of the suppression process appear to be different.