Polyclonal activation of human lymphocytes and induction of cytotoxic lymphocytes by streptococcal preparations.

Polyclonal activation of human peripheral blood lymphocytes (PBLs) in vitro by preparations of Streptococcus pyogenes Su strain (OK-432) and other heat-killed strains was investigated. The streptococcal preparations tested induce a proliferative response of PBLs via interleukin-2 (IL-2)-independent pathways. The proliferative response is accompanied by the generation of lymphoblastic cells (LBCs), which consist of heterologous lymphocyte populations: CD4+ helper type of T cells, and CD4-CD8- double-negative (DN) lymphocytes, including both CD3+ TcR gamma + T cells and CD2+CD3- immature type of T or non-T cell type of lymphocytes. Almost all the LBCs express Leu19, TfR (transferrin receptor), LFA-1 and CD38 (OKT10) antigens, which are expressed on activated T cells, NK cells and some other lymphocytes. The proliferative response of human PBLs is also accompanied by the generation of potent cytotoxic activity against NK-sensitive and -resistant targets. C-dependent cytolysis and cell sorting experiments of OK-432-activated LBCs revealed that both CD3+ and CD3- types of CD4-CD8- DN lymphocytes, but not CD4+ helper T cells, may be major populations responsible for the cytotoxicity induced. On the other hand, CD4-CD8- T cells may be required for the proliferation of PBLs and generation of cytotoxic effector cells. These results suggest that the OK-432 and other streptococcal preparations stimulate the human PBLs in vitro to induce the proliferation/activation of CD4+ T cells, mediating the following generation of DN cytotoxic effector lymphocytes.