The accessory function of phagocytic cells in human T cell and B cell responses

The role of mononuclear phagocytes (M∅) in pokeweed mitogen- (PWM) induced lymphocyte proliferation and generation of immunoglobulin-secreting cells (ISC) was examined. Both responses of human peripheral blood mononuclear cells (PBM) were inhibited when cells were cultured in the presence of silica (< 5μm diameter particle size). In addition, proliferative responses induced by T cell mitogens such as phytohemagglutinin and concanavalin A were also markedly inhibited by silica. The degree of inhibition of mitogen-induced T cell ³H-thymidine incorporation was increased by preincubating PBM with silica before the addition of mitogen. These responses rapidly became resistant to inhibition by silica. By contrast, PWM-induced generation of ISC remained sensitive to inhibition by silica for at least the first 4 days of a 7-day incubation. These results suggested that there were differing requirements for phagocytic M∅ in B and T cell responses. This was confirmed by examining the effect of silica on PWM-induced B and T cell growth. T lymphocyte proliferation became resistant to the effects of silica after the first 24 hr of a 7-day culture. By contrast, B lymphocyte responses remained sensitive to inhibition by silica for as long as 4 days of a 7-day incubation. That silica-mediated inhibition of responsiveness resulted from a selective effect on M∅ was demonstrated in a number of ways. First, when purified cell populations were cultured with silica, killing of monocytes but not B or T cells was observed. Secondly, brief preincubation of PBM with silica followed by density gradient removal of silica and silica-containing cells yielded a population that was markedly depleted of phagocytic cells. After removal of silica-ingesting cells in this manner, PWM-induced lymphocyte proliferation and generation of ISC was abolished but could be entirely reconstituted by addition of M∅ prepared in a variety of ways, but not by interleukin 1-containing M∅ culture supernatants or lymphocytes. Only the phagocytic cells within these M∅ populations were capable of acting as the required accessory cells. These results indicate that the initiation of both B and T cell activation in human PBM requires a phagocytic accessory cell. However, the proliferative response of T cells rapidly becomes relatively independent of these cells, whereas ongoing B cell responsiveness continues to require intact M∅.