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Adenovirus type‐12 tumor antigen. III. Tumorigenicity and immune response to syngeneic rat cells transformed with virions and isolated transforming fragment of adenovirus 12 DNA
Author(s) -
Raška Karel,
Morrongiello Mary Pat,
Föring Bernd
Publication year - 1980
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910260113
Subject(s) - cytotoxic t cell , antigen , immunogenicity , biology , microbiology and biotechnology , antibody , immune system , cell culture , virology , immunology , in vitro , biochemistry , genetics
Tumorigenicity and immunogenicity of two adenovirus 12 (Ad 12)‐transformed cell lines was studied in syngeneic LIS rats. One cell line (RT 2 ), transformed with Ad 12 virions, contains most of the Ad 12 genome and transcribes its E 1 , E 3 and E 4 regions. The other line (RFC 1 ) was transformed with isolated EcoRI‐C fragment of Ad 12 DNA. Both cell lines are equally tumorigenic in newborn rats; in weanling and mature animals the virion‐transformed cells are more tumorigenic as determined by the number of cells required to induce tumors in 50% of animals (TPD 50 ) and by the proportion of “takes” after transplantation of tumor fragments. Serological analysis indicates that antibodies reactive with Ad 12 T‐antigen (product of the E 1 region of Ad 12) appear later than those reactive to other Ad 12 antigen(s) present in RT 2 cells. The “early” RT 2 antibodies are non‐reactive with RFC 1 cells. Sera of RT 2 tumorbearing rats become reactive with RFC 1 , cells and isolated Ad 12 T‐antigen after a period of 1–4 weeks. The sera of RFC 1 tumor‐bearing rats become reactive with transformed cells after a similar period. The RFC 1 sera and the “late” RT 2 sera are cytotoxic to both RFC 1 and RT 2 cells. None of the immunoreactive sera of tumor‐bearing rats are active in antibody‐dependent cellular cytotoxicity (ADCC). The spleen cells of rats bearing RFC 1 , tumors were cytotoxic to both RFC 1 and RT 2 cells. The spleen cells of animals with RT 2 cell tumors, however, did not exert any cytotoxicity against either cell line. When the spleen cells of tumor‐bearing rats were further educated by incubation with transformed cells in vitro, significant cytotoxicity was observed. The spleen cells of rats bearing RFC 1 tumors were equally stimulated in vitro with RFC 1 and RT 2 cells. The cells of rats bearing RT 2 tumors were cytolytic after in vitro exposure to RFC 1 , cells; much less cytotoxicity was observed with cells restimulated in vitro with RT 2 cells. The RFC 1 and “late” RT 2 sera effectively blocked the cytolysis of both RFC 1 and RT 2 cells. The “early” RT 2 antibodies blocked the cellular cytotoxicity against RT 2 cells but not RFC 1 cells. Interestingly, the blocking effect was observed even with the effector cells primed in vivo and educated in vitro with only RFC 1 cells. These results demonstrate that the E 1 gene block of Ad 12 codes for a membrane‐associated antigen active in both humoral and cellular immunity.