The in vitro effect on T cell function of soluble IL-2Rα from advanced ovarian cancer ascites

Activated T cells not only secrete interleukin-2 (II-2) and express cell surface interleukin 2 receptor α (IL-2Rα), but also shed IL-2Rα. This soluble receptor is a truncated form of the membrane-bound p55 receptor with a similar binding affinity. It has been proposed that soluble IL-2Rα (sIL- 2Rα) could negatively modulate local immune response. High levels of sIL- 2Rα have been found in the serum and ascites of ovarian cancer patients. The purpose of this investigation is to determine the amount of in vitro T cell inhibition seen in ovarian cancer ascites that is attributable to high levels of sIL-2Rα. Purified sIL-2Rα at levels up to 100,000 pg/ml was placed in lymphocyte proliferation assays. Soluble IL-2Rα was removed from the ascites of three patients with advanced ovarian cancer. Lymphocyte proliferation assays utilizing phytohemaglutin (PHA) stimulation were carried out with this ascites. Untreated ascites from each patient served as control. Addition of purified sIL-2Rα to lymphocyte proliferation assays failed to demonstrate significant lymphocyte suppression. Addition of ascites to the lymphocyte assays resulted in up to an 80% decrease in lymphocyte proliferation. Neutralization of ascites sIL-2Rα as well as removal of sIL-2Rα via a protein G column failed to reverse any of the observed lymphocyte suppression. We conclude that although sIL2Rα is elevated in ascites of patients with ovarian cancer, it does not account for the profound ascites- induced T cell suppression observed in vitro.