title: Immunotherapy of murine leukemia. XI. differential susceptibility of spleen cells from serum-protected mice to the in vitro immunosuppressive effects of Friend leukemia virus-infected splenocytes.
abstract: It has previously been shown that DBA/2 mice protected against the development of Friend leukemia virus (FLV)4-induced disease by the passive administration of heterologous antisera directed against disrupted virions or the major viral envelope glycoprotein (gp71) fail to undergo the generalized immunosuppression which characterizes FLV leukemogenesis. In the present studies, the susceptibility of spleen cells from serum-protected mice to the immunosuppressive effects of FLV-infected spleen cells has been examined by means of in vitro assays of antibody production and of natural killing (NK). In contrast to the parallel suppression of both functions in FLV-infected mice and their lack of suppression in serum-protected animals, a dichotomy was observed in the in vitro susceptibility of these activities of spleen cells from serum-protected mice to the suppressive effects of virus-infected splenocytes, implying that more than one mechanism of suppression is operative. Thus, the antibody-producing capability of serum-protected splenocytes was not suppressed by FLV-infected spleen cells, this suppression reflecting the activity of infectious virus, while the NK effector function of serum-protected spleen cells was as susceptible as that of normal splenocytes to suppression by virus-infected spleen cells. This suppression of NK activity is mediated by virus-induced suppressor cells and does not involve free infectious virus, in contrast to suppression of antibody production. These results thus indicate that, while serum therapy inhibits the development of the virus-induced NK suppressor cells found in the spleens of progressively infected mice, splenic NK effectors, which are present, demonstrate full susceptibility to the suppressive effects of such independently generated virus-induced suppressor cells. Preliminary attempts at characterizing these NK suppressors in the spleens of FLV-infected mice indicate that they are not eliminated by treatment with antisera directed against T cells, B cells, macrophages or FLV gp71. However, Percoll fractionation of spleen cells from infected mice has revealed the presence of an expanded (as compared to normal spleen cells) population of cells of density 1.077 which demonstrates high in vitro NK suppressor activity, presumably representing the virus-induced suppressor cells measured in this assay. At the present time, the mechanism of the resistance of serum-protected spleen cells' antibody production to suppression by FLV-infected splenocytes (i.e., by FLV itself) remains undefined.
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000032:analysis*; D000920:Antibody-Dependent Cell Cytotoxicity; D000921:Antibody-Producing Cells / Q000276:immunology; D005622:Friend murine leukemia virus / Q000276:immunology; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000382:microbiology
chemical_list: D000912:Antibodies, Neoplasm