Biological properties of suppressive E-receptor factor on lymphokine function

A potent immunosuppressive factor isolated from malignant ascites fluids showed serological cross-reactivity with the E-receptor of human peripheral blood T lymphocytes. Thus, this factor was named suppressive E-receptor (SER) factor. In this study, we examined the effect of this immunosuppressor, SER, on lymphokine functions of human mononuclear cells participating in polyclonal T cell activation. SER is active at nanomolar concentrations in vitro and the inhibitory effect of SER was most pronounced when added at the initiation of stimulation with phytohemagglutinin or anti-T3 antibody. Concomitant with the inhibition on PHA-induced DNA synthesis, lymphocytes that were treated with SER failed to progress beyond G1 phase of cell cycle. These growth-arrested cells did expire after 7 days of culture in vitro. This anti-proliferative effect of SER was more easily demonstrated with normal lymphoid cells in culture than transformed cells or fibroblast cells. SER effectively interfered with the lympho-proliferative properties of interleukin 2 (IL 2) on human peripheral blood mononuclear cells and an IL 2-dependent murine cytotoxic T cell line. However, excess quantities of exogenous IL 2, especially when added in conjunction with IL 1, were able to partially overcome the ability of SER to inhibit T cell proliferation. In contrast to the inhibition on DNA synthesis of human lymphoblasts, expression of IL 2 receptor was only minimally inhibited by SER during the first 24 h of culture (24% inhibition at 12 h and 34% inhibition at 24 h) but it was followed by full expression of IL 2 receptor by 48 h. Thus, SER merely reduced the rate of expression of IL 2 receptor and was not able to inhibit the transcription of new message from activated T lymphocytes. Taken together, these studies indicate that SER acts as a noncytolytic anti-proliferative factor on immune responses that are mediated by T cells. SER appears to act on a relatively late event during T cell activation, perhaps on some portion of the DNA replication pathway.