Effector mechanism of tumor immunity in murine plasmacytoma.
The development of concomitant tumor immunity to plasmacytoma (PC) was previously demonstrated by the detection of splenic immune T-lymphocytes that inhibited the growth of PC in local adoptive transfer (Winn) assay. This immunity was down-regulated by cyclophosphamide-sensitive suppressor T-cells. The effector mechanism was further studied. It was found that immune spleen cells contained no cytotoxic T-lymphocytes as determined by 51Cr release assay. Immune spleen cells, however, exerted a cytostatic effect on PC cells in vitro; coculture of immune spleen cells with PC cells inhibited the [3H]thymidine uptake by tumor cells. No in vitro generation of cytolytic activity was observed. The cytostatic effector cells were found to be radiosensitive, nonadherent, Thy-1+, Lyt-1-2+ lymphocytes that required direct cell-cell contact for cytostasis. Plasmacytoma arising from transplants of mixtures of PC cells and immune spleen cells had a slower growth rate in vivo and incorporated less [3H]thymidine in vitro, findings consistent with the cytostatic effect of immune spleen cells. Studies comparing cytostatic cells assayed in vitro and immune splenic effector cells assayed in vivo (Winn assay) revealed that the former were short-lived (less than 26 days), high dose cyclophosphamide (200 mg/kg) resistant, and cross-reacting to other PC, whereas the latter were long-lived (greater than or equal to 102 days), high dose cyclophosphamide sensitive, and individual tumor specific. Immune spleen cells, however, could inhibit heterologous PC growth in vivo, if the homologous PC were also present. These findings are consistent with the hypothesis that the concomitant tumor immunity in PC involves terminal cytostatic effector T-cells with a broader target spectrum and tumor-specific helper T-cells that are required for clonal expansion and maturation of cytostatic cells in vivo.
Chen
Y H
YH
Veterans Administration West Side Medical Center, Chicago, Illinois.
Anderson
A B
AB
D000818:Animals; D002455:Cell Division; D003520:Cyclophosphamide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D010954:Plasmacytoma / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D003520:Cyclophosphamide