Suppressive Effect of Leukemia Virus-Infected Lymphoid Cells on In Vitro Immunization of Normal Splenocytes2

Abstract

Impaired immunologic responsiveness occurred when spleen cells from Friend leukemia virus (FLV)-infected BALB/c mice were immunized in vitro with sheep erythrocytes and the immune response was d,etermined at the cell level by the hemolytic plaque assay in agar gel. Spleen cells from infected mice also impaired the expected antibody response to sheep erythrocytes by spleen cells trom normal mice immunized in vitro. Asfew as 10⁵ splenocytes from 7- to 28-day FLV-infected mice suppressed the expected antibody response of 5 million spleen cells from normal mice immunized in vitro with sheep erythrocytes. Leukemic spleen cells were immunosuppressivewhen added to normal spleen cells either at culture initiation or as late as 3 days thereafter. However, immunosuppression was even greater when infected spleen cells were mixed with normal spleen cells 2 days before addition of sheep erythrocytes. Bone marrow and thymus cells from FLV-infected mice also decreased the number of antibody-forming cells induced by sheep erythrocytes, but these cell types were less suppressive than splenocytes. Immunosuppression also occurred when infected splenocytes were separated from normal spleen cells by 0.45-)μ cell-impermeable membrane filters, but not by dialysis membranes. The factor(s) from leukemic cells which mediated immunosuppression was either freshly shed virus or a virus-associated factor, since isologous antivirus serum prevented immunosuppression when added to the culture vessels. Cell-free FLV homogenates, though markedly leukemogenic and immunosuppressive in vivo, did not significantly affect the immune response in vitro when added to spleen cell cultures from normal BALB/c mice.