Spontaneous regression of Friend murine leukemia virus-induced erythroleukemia. V. Cell-mediated antivirus immunity in mice undergoing erythroleukemia regression and in leukemic mice

Noninbred ICR/Ha Swiss and inbred N/PLCR mice infected with the regressing Friend murine leukemia virus complex (R-F-MuLV) developed an erythroleukemia that spontaneously regresses. For the determination of whether mice undergoing erythroleukemia regression possess cell-mediated antivirus immunity, splenic lymphocytes were cultured with and without various antigens, and supernatants were harvested and tested for their abilities to inhibit the migration of normal macrophages in the indirect agarose microdroplet macrophage migration inhibition assay. Migration inhibitory factor (MIF) was produced by spleen cells during erythroleukemia regression in response to purified R-F-MuLV, virus-producing cells, and gp70 (a virus structural protein), but not in response to mouse mammary tumor virus, normal spleen cells, or unrelated antigens. This cell-mediated activity was detected in all tested mice with regressed leukemias, some of the leukemic mice, and in none of the normal controls. For an assessment of the significance of the reactivity of leukemia spleen cells in response to virus-specific proteins, MIF production by leukemia spleen cells from conventional, nonregressing Friend murine leukemia virus complex (F-MuLV)-inoculated mice was compared with MIF production by cells from R-F-MuLV-infected leukemic animals. The R-F-MuLV-infected mice exhibited substantially more reactivity than did the F-MuLV-infected mice. The R-F-MuLV-infected animals were also characterized as regressors (those that will undergo leukemia regression) and 'progressors' (those that will not undergo leukemia regression); almost all the spleen cell supernatants from regressors demonstrated MIF reactivity, whereas only about one-half the spleen cell supernatants from progressors contained MIF activity. Therefore, cell-mediated antivirus immunity as measured by the indirect MIF assay appears to be closely associated with regression of erythroleukemia in R-F-MuLV-infected animals.