Immune control of SV40‐induced tumors in mice

The ability of mice to mount a cytotoxic T‐lymphocyte (CTL) immune response to SV40 T‐antigen is determined by the H‐2 haplotype of the host; H‐2b and k mice are high responders and H‐2d mice are low responders. Mice of these 3 H‐2 haplotypes were challenged with SV40 and their ability to generate and sustain an antibody response to SV40 T‐antigen was found to be equivalent. To investigate the role of the different components of the host immune response in controlling growth of SV40‐induced tumors, the tumorigenic potential of freshly established cell lines, obtained by SV40 transformation of cells from normal tissues of inbred strains of mice of 6 H‐2 haplotypes, was assessed. Each cell line was tumorigenic in athymic and newborn mice but not in adult syngeneic immunocompetent mice. Cells from these initial SV40‐transformed lines were then passaged in athymic (nu/nu) mice, re‐established in vitro and again transferred into syngeneic animals. Transfer of H‐2d SV40 transformants to low or non‐responder mice of the H‐2d haplotype resulted in tumor formation in some animals. Cells derived from these tumors expressed both the viral encoded T‐antigen and the H‐2Dd restriction element. Furthermore, the proportion of animals with tumors varied with the strength of their CTL‐responsiveness to SV40 T‐antigen in association with H‐2Dd. Therefore, in H‐2d animals, tumor cell growth appears to result from escape of cells from inefficient CTL surveillance. No tumors were formed by transfer of the in vivo selected H‐2b or H‐2k SV40 transformants to syngeneic high‐responder mice. We therefore investigated the role of CTL in the selection of SV40‐transformed cells able to escape immune surveillance. Under conditions of stringent immune selection by CTLs, tumorigenic cells that no longer expressed the relevant H‐2 class‐I restriction element were obtained. Although interaction between the various immune effector mechanisms may play a role in the recognition and elimination of SV40 transformants, our results were consistent with the hypothesis that the SV40‐specific CTL response is the predominant control of SV40 tumor growth.