| Abstract: |
Infection of CMS5 tumor cells with retroviral constructs containing interleukin-2 (IL-2) cDNA and selection in medium supplemented with G418 resulted in the isolation of clones which secreted IL-2. Whereas injection of parental tumor cells resulted in progressive tumor growth, tumor cells secreting high levels of IL-2 were rejected. Furthermore in animals vaccinated with IL-2-secreting cells, the immunosuppression associated with the inoculation of parental tumor cells did not develop, and these animals resisted a challenge with viable tumor cells. To better understand the functional differences in the anti-tumor responses of immune and tumor-bearing mice which are at the basis for these diverse responses, we used an in vitro model to analyze interactions between splenic lymphocytes and tumor cells. Spleen cells isolated from either tumor-bearing or immune mice proliferated vigorously when cultured alone for 6 days, but much less in the presence of parental tumor cells. This effect could not be transferred with supernatant from tumor cell lines. Spleen cells from tumor-bearing mice remained unresponsive, while those from immune mice proliferated well in response to IL-2-secreting tumor cells. Only spleen cells from immune animals were able to develop cytotoxicity against CMS5 cells following in vitro restimulation. These results are consistent with the interpretation that exposure to parental tumor cells inhibited cell-mediated anti-tumor responses by a mechanism that involved cell-to-cell contact. Furthermore, the development of this inhibition was dependent on a failure of responding cells to generate sufficient amounts of IL-2, since it could be prevented or overcome, at least in part, by locally secreted IL-2. |
