Blocking of T cell activation at the G1A/G1B interface of the cell cycle and prevention of expression of interleukin 2 receptors by alloactivated suppressor T lymphocytes.

Abstract

Suppressor T (Ts) leukocytes affect various immune reactions including the activation of T cells by alloantigens. It is, however, not known where Ts interfere with the sequence of events supporting T cell activation and proliferation. In the present studies, alloantigen selective Ts were activated by in vitro priming with heat-inactivated allogeneic leukocytes in the mixed leukocyte reaction (MLR). Such Ts, or a soluble factor thereof, were shown to interfere with the progression of MLR responder cells from the G1A to the G1B phase of the cell cycle. In the presence of Ts, most MLR responder cells did not express interleukin 2 receptors, although a small minority of cells constantly escaped Ts inhibition. Moreover, Ts modified MLR contained only minor interleukin 2 (IL-2) bioactivity suggesting also an effect of Ts cells on IL-2 synthesis. The addition of exogenous IL-2 to Ts modified MLR increased 3H-thymidine incorporation although Ts retained the capacity to regulate the proliferative response in a dose-dependent fashion. Phenotypic analysis of allostimulated T cells proliferating in the presence of preformed Ts and exogenous IL-2 revealed a conspicuous failure of T helper cells to proliferate in response to alloantigen despite the presence of very high IL-2 concentrations.