Properties of Murine Leukemia-Associated Suppressor Cells

Abstract

Abstract The spleens of BALB/c mice bearing leukemia induced with Moloney leukemia virus contain cells capable of inhibiting the antibody response of normal immunocompetent lymphocytes in Marbrook culture vessels. The immunosuppression requires contact between the cells and appears to be mediated by leukemia-associated suppressor cells rather than by the leukemic cells themselves. Thymus-dependent antibody responses to sheep red blood cells (RBC), horse RBC or trinitrophenol coupled to ovalbumin (TNP-OVA) were inhibited proportionally to the number of suppressor cells added. In contrast, thymus-independent responses to Vibrio cholerae lipopolysaccharide and to TNP coupled to Ficoll were either unaffected or suppressed only with a high number of suppressor cells. The leukemia-associated suppressor cells from BALB/c mice (H-2d) inhibited the anti-sheep RBC response of syngeneic lymphocytes and of allogeneic DBA/2 lymphocytes bearing the H-2d haplotype but failed to inhibit lymphocytes from other allogeneic strains DBA/1 (H-2q), C57BR (H-2k), A (H-2a), and C57BL/10 (H-2b). Experiments with lymphocytes from congenic strains carrying various H-2 gene complexes on the B10 genetic background confirmed that the suppressor effect is restricted by genes in the H-2 complex. Further mapping suggested that the suppression requires identity in the K region between the suppressor and the responder cells. The inability to suppress the allogeneic, H-2 different lymphocytes was retained even when a majority of the leukemic, virus-producing cells were removed from the spleen cell suspension by using a specific cytotoxic antiserum. There was no correlation between permissivity of lymphocytes to infection by the Moloney leukemia virus in vitro and between their inhibition by the suppressor cells. Thus, the nonspecific (polyclonal) leukemia-associated suppressor cells preferentially inhibit helper T cells and the suppression involves a specific interaction with product(s) of K region genes on the surface of the responder cells.