Adoptive immunity in mice challenged with L1210/DTIC clones
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Abstract:
New antigenic specificities, not detectable on parental cells, have been induced by many investigators in mouse lymphomas by treatment with the antitumor agent 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The antigens are transmissible, after withdrawal of the drug treatment, as an inheritable character. The mechanism of induction, the molecular nature, and the number of the new antigenic specificities have not been completely elucidated. Four clones from murine leukemia L1210 isolated and expanded in vitro were treated in vivo with DTIC and the new sublines were studied in detail. The four drug-treated sublines studied exhibited strong immunogenicity since they were rejected by syngeneic animals. Immunosuppressed animals challenged with 10(7) A/DTIC or P/DTIC cells were reciprocally protected by the adoptive transfer of spleen cells from donors that had rejected a lethal challenge of A/DTIC or P/DTIC clone. In a similar fashion, the adoptive transfer of spleen cells obtained from animals that had rejected the Q/DTIC or the R/DTIC clones protected immunosuppressed mice challenged with Q/DTIC or R/DTIC cells. No antitumor activity was observed in cross-protective schedules other than those indicated. It was been concluded that (a) the L1210 leukemia line does not have antigenic cells, (b) four DTIC-treated clone sublines were rejected by compatible hosts, and (c) two mutually exclusive sets of antigens were expressed in four antigenic clone sublines.
Insights
Treatment with 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) induced new antigens in mouse leukemia L1210. These DTIC-induced antigens were immunogenic and demonstrated mutually exclusive expression patterns.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- New antigenic specificities can be induced in mouse lymphomas by 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC).
- These induced antigens are transmissible and heritable after drug withdrawal.
- The precise mechanism, molecular nature, and number of these specificities remain unclear.
Purpose of the Study:
- To investigate the immunogenicity and antigenic characteristics of DTIC-treated murine leukemia L1210 sublines.
- To determine if DTIC induces new, detectable antigens on leukemia cells.
- To analyze the inheritance and expression of these induced antigens.
Main Methods:
- Four clones of murine leukemia L1210 were treated in vivo with DTIC.
- The resulting sublines were studied for immunogenicity in syngeneic animals.
- Adoptive transfer of spleen cells was used to assess cross-protection in immunosuppressed mice.
Main Results:
- DTIC-treated sublines (A/DTIC, P/DTIC, Q/DTIC, R/DTIC) exhibited strong immunogenicity and were rejected by syngeneic hosts.
- Specific reciprocal cross-protection was observed between A/DTIC and P/DTIC, and between Q/DTIC and R/DTIC.
- No cross-protection was found between the two pairs of sublines, indicating distinct antigenic sets.
Conclusions:
- The parental L1210 leukemia line lacks detectable antigenic cells.
- Four DTIC-induced antigenic sublines were successfully generated and demonstrated immunogenicity.
- Two mutually exclusive sets of antigens were expressed by the four DTIC-treated antigenic clone sublines.