Immunoregulatory functions of cultured human T lymphocytes

Twenty continuous cultures of human T cells (CTC) (15 from normal individuals and five from patients with T cell malignancy) growing in the presence of PHA-stimulated lymphocyte conditioned medium were studied for their ability to participate in the regulation of the in vitro immunoglobulin (Ig) production induced by five polyclonal activators, pokeweed mitogen (PWM), Epstein-Barr virus (EBV), Nocardia opaca water-soluble mitogen (NWSM), streptolysin O (SLO), and staphylococcl phage lysate (SPL). The CTC did not produce significant amounts of Ig in the presence of any polyclonal activator. One out of 15 CTC examined showed helper activity of moderate degree when co-cultured with B cells rigorously depleted of T cells in PWM-driven Ig biosynthesis. Two of the other CTC helped minimally. Nine of 20 CTC examined (8 of 15 from normal individuals and 1 of 5 from patients with T cell malignancies) were found to have marked suppressor cell activity when co-cultured with normal lymphocytes in the PWM-induced Ig production system and four had moderate or variable suppressive effect. This suppression was apparently not due to simple "overgrowth" or nonspecific toxic effects of CTC because (1) the CTC did not proliferate when cultured without conditioned medium, (2) the CTC did not suppress Ig production when they were added 3 days after the beginning of the 12-day cultures, (3) the CTC did not show cytotoxic activity against normal T and B cells, and (4) the CTC did not inhibit tritiated thymidine incorporation into PWM- or EBV-stimulated lymphocytes when mixed with them at the onset of culture. Ig production induced by EBV or NWSM, which are relatively T cell-independent polyclonal activators, was suppressed significantly T cell-independent polyclonal activators, was suppressed significantly by only one out of nine and one out of six CTC examined, respectively. Four clones produced by a limiting dilution method from one suppressor CTC suppressed PWM-driven Ig synthesis as markedly as the uncloned suppressor CTC. Such CTC may be of considerable value in studies of the mechanisms involved in the regulation of immunoglobulin biosynthesis and in the preparation of antisera to T cell subsets.