Immunosuppression by Spleen Cells from Moloney Leukemia

Abstract

Abstract The mechanism by which spleen cells from mice bearing established Moloney leukemia suppress the in vitro anti-SRBC PFC response and the mitogen-induced proliferative response was investigated. Suppression of the PFC response was clearly evident when leukemic spleen cells (SMuLV) were mixed with normal responder spleen cells (SN) at a ratio of 1:10. The suppressor cells were most effective when added to the responders during the first 24 to 48 hr of culture. Similarly, suppression was seen when responders were treated with homogenate fractions prepared from SMuLV. No suppression of the PFC response was demonstrated when responder cells were mixed with supernatants harvested from cultures of SMuLV. In contrast, the incorporation of 3H-thymidine by mitogen-stimulated B and T cells was inhibited by supernatants collected from cultures of both SN and SMuLV, however, this suppressive effect was abrogated after dialysis of the supernatants. In addition, responder cells were unaffected when separated from suppressors by a 100-nm Millipore filter in double Marbrook tissue culture chambers. The results of this study lend considerable support to the hypothesis that suppression in the Moloney leukemia model system is not due to the effect of extracellular mediators, but rather is the result of direct cellular interactions between the suppressor and responder cells. The exact nature of the suppressor cell has yet to be determined.