Mechanism of decline of natural killer cell activity in Corynebacterium parvum-treated mice: inhibition by erythroblasts and Thy 1.2+ lymphocytes.
Injection of (C57BL/6 X DBA/2)F1 mice with Corynebacterium parvum (CP), iv, resulted in a depression of splenic natural killer (NK) cell activity 7-17 days after treatment. This decline in reactivity was accompanied by an increase in splenic tumor-binding cells and a decrease in cytotoxic tumor-binding cells as evaluated in a single-cell assay. Morphologic analysis indicated that the increased tumor-binding cells following CP injection were due to erythroblasts binding to YAC-1 tumor cells. With the use of a double-fluorescent binding technique, nonlytic tumor-binding cells of CP-treated mice inhibited NK cytotoxicity of normal syngeneic mice by competing with effectors for binding to tumor cells. Removal of erythroblasts by hypotonic shock treatment eliminated this competition and significantly improved the lytic capacity of CP-treated mice, thus indicating that erythroblasts contributed to the suppression of NK activity in these mice. The presence of a second inhibitory mechanism in CP-treated mice was found following asialo GM1 treatment or Percoll density gradient separation of erythroblast-depleted CP splenocytes; this inhibitory population was identified as Thy 1.2+ lymphocytes. Further analysis of the mechanism of suppression indicated that it was mediated by a soluble factor. In addition to the presence of suppressor cells, CP-treated mice displayed a decrease in splenic large granular lymphocyte content, which may also contribute to their NK deficiency.
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D004900:Erythroblasts / Q000502:physiology*; D005260:Female; D007166:Immunosuppressive Agents / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology; D011425:Propionibacterium acnes / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D018800:Thy-1 Antigens