Abstract
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 anti-tumour 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 tumour-bearer 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 anti-tumour 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.
Highlights
In this paper we describe the use of the Winn assay (Winn, 1961) to study the development and later suppression of splenic T cell-mediated immunity in animals inoculated with the MC-2 tumour
The metastasizing MC-2 fibrosarcoma which is syngeneic for BALB/c mice has been described previously (Finlay-Jones et al, 1980)
Anti-MC-2 activity in the Winn assay was detected in spleen cells of excision-immunized (Table IA) and early-stage tumour-bearing mice (Table iB)
Summary
Age-matched, female BALB/c mice were used in all experiments. Host animals used in the Winn assays were 2-12 months old. Five to eight days later tumours of 30-90mg weight were excised under pentobarbitone sodium (Nembutal, Abbott Labs., Sydney, Australia) anaesthesia. These mice were rechallenged s.c. with 105 MC-2 cells 2-4 weeks later. In some experiments immunized mice were given a further challenge dose of 105 MC-2 cells several months later. Spleen cells from excision-immunized or tumourbearing mice were mixed with MC-2 cells and inoculated s.c. into sublethally irradiated recipients at a final dose of 106 spleen cells: 104 tumour cells/mouse.
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