Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation

T-B and T-T interactions involved in the regulation of PWM-triggered human B cell differentiation were studied in vitro. Functionally distinct human T cell subsets were isolated by C-mediated lysis by using the monoclonal antibodies OKT4 and OKT8. Graded numbers of either untreated or irradiated T cell subsets were added to autologous B cells, and total antibody synthesis was measured after 5 to 6 days of culture by using a highly sensitive reverse hemolytic plaque assay. The data indicate that a) the helper activity that is exclusively contained within the OKT4 ⁺ population is radiosensitive. Only at high T/B ratios can this radiosensitivity be overcome; b) the OKT8 ⁺ population contains radiosensitive cells important in suppressing B cell differentiation, and c) the suppression induced with OKT8 ⁺ cells requires the presence of radiosensitive OKT4 ⁺ cells. Thus, OKT8 ⁺ cells added to cultures containing B cells and irradiated OKT4 ⁺ cells do not suppress the PFC response. Addition of unirradiated OKT4 ⁺ cells to these cultures permits reexpression of suppression by OKT8 ⁺ cells. It is concluded that two radiosensitive cells, one within the OKT4 ⁺ population and the other within the OKT8 ⁺ population, collaborate to induce suppression. Possible mechanisms for this suppressive interaction including induction of suppressor precursor cells within the OKT4 ⁺ population or inhibition of OKT4 ⁺ helper cells by OKT8 ⁺ cells are discussed.