- A simian virus 40 (SV40) transplantable tumor was established in high responder C57bl/6 mice using a syngeneic, SV40-transformed cell line. These tumor cells synthesized both the SV40 large T and small t antigen and expressed the SV40 transplantation rejection antigen (TrAg) at their cell surface. While immunization of mice with SV40 was found to inhibit the growth of the newly derived tumor, this immunity could be overcome when large numbers of tumor cells were used to challenge mice. Those tumors which arose in the SV40 immunized mice retained their expression of SV40 large T and small t antigen but exhibited a reduced susceptibility to in vitro lysis by SV40-specific cytotoxic T lymphocytes (CTL).
To study further the relationship between SV40 TrAg and the expression of other SV40 early gene products, the SV40 tumor rejection response in C57Bl/6 mice was examined using a syngeneic, polyoma-induced tumor cell line that had been secondarily transformed in vitro by SV40. These SV40:polyoma double transformant cells are stably transformed by SV40 and express SV40 large T, small t antigen and SV40 TrAg. While immunization of mice with SV40 was found to inhibit the growth of low numbers of double transformant tumor cells, larger numbers gave rise to tumors which no longer expressed SV40 TrAg. The loss SV40 TrAg expression was found to be concomitant with the loss of expression of both large T and small t antigen.
The immune effector cells mediating the in vitro and in vivo SV40 immune response were characterized. Two distinct T lymphocyte populations were found to be responsible for the in vitro lysis of SV40-transformed cells, an Lyt 1('+),2('+) CTL which is present in the spleens of SV40 immunized mice 9 days post immunization and an Lyt 1('-),2('+) CTL which is generated by in vitro stimulation of SV40 immune spleen cells or in vitro culture of immune lymph node cells. While the Lyt 1('-), 2('+) CTL can be derived from Lyt 1('-),2('+) noncytotoxic memory cells, whether the Lyt 1('+),2('+) CTL differentiates into an Lyt 1('+),2('+) CTL during in vitro stimulation is not known. The adoptive transfer of SV40 tumor immunity from SV40 immune mice to normal mice was found to require the presence of an Lyt 1('+),2('+) lymphocyte. Neither Lyt 1('-),2('+), Lyt 1('+),2('-) or a combination of the two lymphocyte populations were capable of transfering SV40 immunity.
- Dissertation Note:
- Ph.D. The Pennsylvania State University 1982.
- Source: Dissertation Abstracts International, Volume: 43-07, Section: B, page: 2155.
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