In vivo and in vitro immunomodulatory ability of streptococcal mitogen: effects on adjuvant disease in the rat; on homograft rejection in the mouse; and on the appearance of Ia antigens on human T lymphocytes.

Streptococcal mitogen (SM) is an extracellular product of group A streptococci, nonspecifically mitogenic for both B and T lymphocytes. The mitogenic activity of SM is resistant to digestion with trypsin, to heating at 100 degrees C for 5 min and to treatment with dithiothrietol. The proliferative response of lymphocytes from patients with a history of rheumatic fever is similar to that of lymphocytes from healthy donors when stimulated with optimal concentrations of SM, but is significantly reduced when low doses of SM are used. Rats were treated with s.c. injections of SM for 21 days at various times from the injection with adjuvant: both primary and secondary reactions in the joints were depressed, more so with pretreatment and early treatment. A similar pattern of response was observed in the survival of A tail skin grafts on the flank of CBA mice: a strain combination with strong H-2 incompatibility. Human T lymphocytes stimulated with SM acquired Ia antigens and the ability to stimulate allogeneic and autologous lymphocytes in mixed lymphocyte reactions. An involvement of Ia antigens in these reactions was indicated by the specific block by monoclonal antibodies to human Ia antigens. T lymphocytes may acquire Ia antigens following exposure to an appropriate antigen. If this occurs following a streptococcal infection, our in vitro findings suggest that Ia bearing T cells may play a role in the immunopathological events which can follow a streptococcal infection. This in vitro system may be a useful model to analyse these immunopathological events and to develop therapeutic approaches in autoimmune conditions. The in vitro findings, together with the observed suppressive effects on the in vivo models described, indicate that SM is a valuable means for study and manipulation of a variety of immune responses.