Summary The MC-2 fibrosarcoma, which is a transplantable tumour syngeneic for BALB/c mice, metastasizes to lymph nodes draining subcutaneous inoculation sites, and also to the lungs. T cell-mediated immunity was detected in Winn assays using spleens from excision immunized mice. T cell-mediated antitumour immunity was also detected in spleens from mice with small tumours but disappeared as the tumour burden increased. Protective immune spleen cell activity in the Winn assay was inhibited by prior addition of spleen cells from mice with large tumours, causing increased tumour incidence. Splenic metastases occasionally occurred in the MC-2 model, but were not demonstrable by bioassay in any of the experiments detecting splenic suppressor cell activity. In vivo protective activity was restored to advanced-stage tumourbearer spleens by whole-body ionizing irradiation (0.5 and 2.5 Gy) of donor mice 15 h before sampling. Spleen cells from mice with small tumours remained protective after 1.5, 2.5 and 4.0 Gy of irradiation in vivo. These results are consistent with the properties of radiosensitive suppressor T cells. In contrast to reports in other tumour models, suppressor cells were not detected until late in the course of MC-2 development. This is surprising in view of the aggressively metastatic nature of MC-2. It is postulated that modulation of the antitumour immune response by the suppressor cells is associated with metastasis in this tumour model. The late appearance of both suppressor cells and metastatic cells in the spleen may reflect similar processes occurring earlier in regional lymph nodes.
Summary In Winn assays, T cells from donors immunized by tumour excision, or from mice with small tumours, mediate rejection of the metastasizing murine fibrosarcoma MC‐2. As the mean size of primary tumours in spleen donors increases, the strength of anti‐tumour activity declines, until it is frequently undetectable in spleen cells from mice with very large tumour burdens. Loss of splenic anti‐tumour activity is coincident with the appearance of cells capable of suppressing an otherwise protective anti‐tumour response in Winn assays. This paper defines the phenotypes of T cells mediating immunity against MC‐2. Eleven or more days after tumour inoculation the proportions of tumour‐bearer splenic leucocytes expressing Ly 1.2 (CD5), Ly 2.2 (CD8a) or L3T4 (CD4) surface antigens were significantly less than similar preparations from normal animals. Depletion of Ly 1.2+ or L3T4+ cells from spleen cells of donors with small tumours, or from donors immunized by tumour excision, diminished protection in the Winn assay. Depletion of Ly 2.2+ cells from these donors had no effect on immunity. In contrast, spleen cells taken from donors with large tumours lost all anti‐tumour activity if pretreated with any one of anti‐Ly 1.2 or anti‐Ly 2.2 or anti‐L3T4 antibodies in the presence of complement. These results suggest that cells bearing the Ly 2.2 marker may be important to weak immunity remaining in the spleens of mice with large tumours, but are not critical to strong immunity generated early in tumour growth, nor to that following tumour excision. That is, in addition to an Ly 1.2+, Ly 2.2−, L3T4+ spleen cell subset also seen early in the growth of the MC‐2 tumour, a cell population which expresses the Ly 2.2 marker and which is important to anti‐tumour immunity emerges late in tumour growth.
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