Generation of antisuppressor T cells for alloreactive cytotoxic T lymphocytes

This study demonstrated that antisuppressor T cells (T/sub AS/) were generated in allogeneic mixed lymphocyte culture (MLC) when supplemented with a conditioned medium containing T cell differentiation factor (CM-TCDF). CM-TCDF was shown to efficiently restore the alloreactive cytotoxic T lymphocytes (CTL) response in accessory cell-depleted MLC. These findings suggested that bulk-cultured MLC might contain different populations of immunoregulatory cells in addition to CTL effectors. These immunoregulatory cells provide on or off signals to turn on or to turn off the lytic machinery of CTL. The suppressor T cells (T/sub s/) generated in MLC might provide the off signal to CTL that resulted in the termination of their cytotoxic activity after 7 days of culturing. When CM-TCDF was supplemented in MLC, the authors found that T/sub AS/ were generated. T/sub AS/ could efficiently abrogate the suppressor activity of anti-allo-T/sub S/, but they had no effect on the anti-self veto cell activity. Both the T/sub AS/ and T/sub S/ activities were allospecific. The precursors and effectors of T/sub AS/ were both found to be L3T4+ cells, whereas the T/sub S/ effectors were Lyt-2+ cells. Generation of T/sub AS/ was completely blocked by αL3T4 antibody and partially blocked by αThy-1 antibody. T/sub AS/ might represent a separate set of immunoregulatory cells that provide an off signal to the T/sub S/, which allowed the lytic machinery of the CTL to remain active and, thus, to maintain their cytotoxic activity for a prolonged period of time. Cell-mediated cytotoxicity was measured with [125I] iododeoxyuridine release