Differential regulation of activation-associated receptor expression on CD4- and CD8-positive T lymphocytes by...

We have demonstrated by two-color flow cytometry that allosensitized human suppressor T cells thwart progression of alloactivated T cells into the G1B stage of the cell cycle, and consequently prevent the expression of transferrin receptors on the majority of alloreactive MLR responder cells (P less than 0.005). Suppressor cells inhibit transferrin as well as interleukin-2 receptor expression on both CD4- and CD8-positive responder cells. The addition of 20 U/ml of recombinant interleukin-2 at the initiation of suppressor coculture bioassays completely neutralizes the suppressive effect of suppressor T cells exerted on CD8-positive responder T cells, but does not restore expression of transferrin and interleukin-2 receptors on CD4-positive T cells. Hence, CD4-positive T cells are the direct target of the suppressor cells, while inhibition of transferrin and interleukin-2 receptor expression on CD8-positive T cells results from reduced levels of interleukin-2 in suppressor cell-regulated cultures. In suppressor cell modified mixed lymphocyte reactions supplemented with exogenous interleukin-2 CD8+/CD28- responder cells proliferate preferentially. It is apparent that mixed lymphocyte reactions supplemented with allosensitized suppressor cells cultured in an interleukin-2-rich environment create a milieu that permits the preferential expansion of T cells with suppressor effector phenotype. This in vitro system provides a convenient model in which to cultivate activated CD8+/CD28- T cells.