The Suppression of Mitogen- and Alloantigen-Stimulated Peripheral Blood Lymphocytes by Cultured Human T Lymphocytes

Abstract

Cultured T lymphocytes (CTC), which were grown in medium containing a growth-promoting factor from supernatants of pooled, allogeneic, PHA-stimulated PBL, were examined for their ability to suppress mitogen-induced proliferative responses or MLC reactions. This suppressor activity was assayed by adding the CTC to either Con A- or PHA-treated lymphocytes or to a mixed lymphocyte culture. The incorporation of ³HTdR into nuclear protein was then quantitated at the end of the culture period and compared to the control ³HTdR uptake values. The addition of CTC significantly suppressed thymidine incorporation in both the mitogen- and alloantigen-stimulated cultures. This suppressed thymidine uptake was not due to competitive inhibition by cold thymidine released into the culture medium by the CTC. Likewise, this suppressor activity could not be accounted for by a “crowding” effect of the added CTC or by the depletion of nutrients from the culture medium by metabolizing CTC. CTC autologous to the responding normal lymphocytes were as effective in suppressing the mitogen and alloantigen responses as allogeneic CTC, indicating that the observed suppression by CTC could not be explained by the cytotoxicity by alloantigen-sensitized or polyclonal-activated CTC. Viable and irradiated CTC were equally effective in suppressing the Con A response. However, in the response to allogeneic cells, irradiating the CTC completely abrogated the suppressor effect. This model system provides a good approach for studying suppressor activity of human T lymphocytes that are not contaminated by other types of cells with suppressor potential, such as monocytes. In addition, this system should provide a means to evaluate ways by which this T cell suppressor activity can be modulated.