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Naturally occurring cell-mediated cytotoxicity against simian virus 40-transformed 3T3 murine tumor cells
Abstract:
The tumorigenicity and host protective mechanisms induced by simian virus 40 (SV40)-transformed 3T3 cells (SV403T3) were evaluated in syngeneic BALB/c mice. Tumors were regularly produced by sc inoculation of SV403T3 cells; the incidence, latent period, and survival were proportional to the size of the initial inoculum. With the use of an in vitro 18-hour 51Cr cytotoxicity assay, spleen cells from normal mice showed a dose-related killing activity against the SV403T3 cells. At an effector cell-to-target cell ratio of 200:1, the average lysis was 56 +/- 6%. This reaction appeared specific for the virally transformed targets; the mean lysis of parent 3T3 cells was 23 +/- 5%. Effectors were resistant to anti-theta serum and not removed by adherence to plastic or nylon wool. Tissue distribution studies indicated that these effectors were present in high concentrations in spleen, bone marrow, lymph nodes, and peritoneal cavity. Low levels of activity were associated with cells from the thymus. In the present studies specific T-cell cytotoxicity against the SV403T3 cells could not be demonstrated. Animals challenged with nonviable SV403T3 cells prior to tumor cell inoculation did not show increased in vivo resistance. In parallel, the in vitro cytotoxicity of animals inoculated with SV403T3 tumor cells showed no heightened cell killing compared to the cytotoxicity of normal controls.
Insights
Simian virus 40 (SV40)-transformed 3T3 cells induce tumors in mice. Normal mouse spleen cells exhibit cytotoxic activity against these transformed cells, but T-cell responses were not observed.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Simian virus 40 (SV40) is a DNA virus known to cause tumors in various animal models.
- SV40-transformed cells (SV403T3) provide a model for studying tumor development and host immune responses.
Purpose of the Study:
- To evaluate the tumorigenicity of SV403T3 cells in BALB/c mice.
- To investigate the host protective immune mechanisms against SV403T3 tumors.
Main Methods:
- Tumorigenicity was assessed by subcutaneous inoculation of SV403T3 cells in BALB/c mice.
- In vitro 51Cr cytotoxicity assays were used to evaluate spleen cell activity against SV403T3 and parent 3T3 cells.
- Effector cell characterization involved resistance to anti-theta serum and adherence properties.
- Tissue distribution of cytotoxic cells was analyzed.
Main Results:
- SV403T3 cells regularly produced tumors, with incidence and severity proportional to inoculum size.
- Normal mouse spleen cells demonstrated dose-dependent cytotoxicity against SV403T3 cells, with limited activity against parent 3T3 cells.
- Cytotoxic effector cells were found in spleen, bone marrow, lymph nodes, and peritoneal cavity, but not significantly in thymus.
- Specific T-cell cytotoxicity against SV403T3 cells was not detected.
- Pre-challenge with nonviable SV403T3 cells or inoculation with tumor cells did not enhance in vivo or in vitro cytotoxicity.
Conclusions:
- SV403T3 cells are tumorigenic in BALB/c mice.
- A non-T-cell mediated cytotoxic mechanism exists in normal mouse spleen cells against SV403T3 cells.
- The host immune system does not mount a specific T-cell response against established SV403T3 tumors in this model.