Inhibition of in vitro lymphocyte function by a soluble AKR leukemic suppressor factor

A soluble suppressor factor(s) found in the serum of AKR mice bearing lymphocytic leukemia (AKR-LSF) has previously been shown to inhibit PHA-induced spleen cell proliferation. In this study we have further characterized the biological activity of the leukemic mouse serum (LMS) in vitro. The LMS inhibits spleen cell proliferation in an MLC as well as generation of functional CTL. The inhibition of CTL generation was not specific since CTL activity resulting from responder and stimulator combinations of various H-2 haplotypes was inhibited. LMS did not inhibit CTL- or NK-mediated cytolytic activity. These results suggested that LMS inhibits lymphocyte proliferative responses but has no effect on cytolytic function. Furthermore, responder cells which had been inhibited by LMS in a primary MLC, washed, and restimulated were able to express CTL activity indicating that the suppression by LMS is reversible. The suppressive effect of LMS is occurring at an early stage of CTL generation since LMS was inhibitory when added on Day 0 or Day 1 but not on Days 2, 3, or 4 of the MLC. Addition of IL-2 did not remove the inhibition by LMS as measured in a PHA proliferative assay. These results suggested that the suppression is not due to a lack of IL-2 but to an inability of the cells to either bind or utilize IL-2.