Activation of immune regulatory circuits among OKT4+ cells by autologous mixed lymphocyte reactions.

We examined the nature of an autologous mixed lymphocyte reaction (AMLR) using T cell subsets defined by monoclonal antibodies. Cells capable of proliferating in the AMLR were demonstrated to reside in an OKT4+, but not an OKT8+, cell subset. With regard to the role of the T cell subsets recoverable from AMLR in the immune regulation, OKT4+ cells isolated from cells that had been activated for 3 days in AMLR did help pokeweed mitogen (PWM) stimulated immunoglobulin synthesis by autologous B cells. However, the OKT4+ cells activated for 6 days in AMLR exerted strong suppressor activity for PWM-induced immunoglobulin synthesis. Irradiation with 1,500 rad on activated OKT4+ cells in AMLR for 6 days not only eliminated the suppressor function but allowed for re-emergence of helper function. Cells exerting suppressor activity alone were recovered from OKT8+ cells stimulated with or without autologous non-T cells. These data suggest that OKT4+ cells activated in AMLR contain two functionally different subsets; one as helper cells and the other as suppressor cells. In addition, the emergence of OKT4+ suppressor function follows activation of the OKT4+ helper population, suggesting that a part of AMLR reflects a mechanism of 'feedback suppression' among OKT4+ cells.