Alternate Changes of Surface Antigen(s) in Adenovirus Type 12‐Transformed and Tumor Cells1

Japanese Journal of Microbiology

Uetake

1974

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Newborn hamsters were inoculated with human adenovirus type 12 (Ad 12) within 24 hr of birth for tumor induction, and 15 days later, intercurrently immunized with Ad12-infected cells (KB; HeLa; FL; HEK; MoE; HaE).Tumor development was then observed for 75 days thereafter. Tumor formation was prevented at a statistically significant level by immunization with any of the above-mentioned infected cells. The immunization was effective even with abortively infected cells (HaE; MoE) or with cells infected in the presence of 5-fluorodeoxyuridine. The induced immunity was Ad 12-specific, since neither cells infected with Ad2, Ad7 or Ad18 nor CV-1 cells infected with SV40 were able to prevent tumor formation. The most plausible explanation to these findings could be that Ad 12-specific tumor-specific transplantation antigen is induced on the surface of freshly virus-infected cells and it is responsible for induction of specific cellular immunity. This gives an experimental support to our hypothesis on the mechanism of induction of cellular immunity against virus infections and to the hypothesis proposed by Habel and by Sjogren to explain the immunoresistance against tumor cells induced following viral immunization.

Section: Discussionmentioning

confidence: 99%

Tumor‐Specific Transplantation Antigen Activity of Freshly Adenovirus‐Infected Cells

Nakajima

Japanese Journal of Microbiology

Uetake

1974

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“…In these respects we have done some experiments, of which results will be described in a separate paper [14].…”

Section: Discussionmentioning

confidence: 99%

Detection of a Specific Surface Antigen(s) in Adenovirus Type 12‐Transformed Cells by Fluorescent Antibody Technique

Japanese Journal of Microbiology

Nakajima

Uetake

1973

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A surface antigen(s) was detected in adenovirus type 12 (Ad12)-transformed cells by fluorescent antibody technique. The antigen was revealed by antisera of mice and rabbits immunized with the virus, and by those of rabbits immunized with conditioned medium from cell cultures carrying the surface antigen. The antigen was specific for the Ad12-transformed cells, since it was found only in the Ad 12-transformed cells regardless of the animal species and not in any other cells, including SV40-and polyoma virus-transformed cells. The antigen was distinct from the Ad12-specific viral and T antigens, since the sera of rabbits immunized with the conditioned medium contained little or no detectable antibodies to the latter two antigens. On the contrary, the surface antigen was not detected in any tumor cells induced by Ad12 by the above antisera, and no detectable antibody to the surface antigen was produced in mice immunized with the tumor cells.In transformed or tumor cells induced by small oncogenic DNA viruses such as papilloma, polyoma, and SV40 viruses, the appearance of specific surface changes was well documented. One of them, the tumorspecific transplantation antigen (TSTA) is defined by in vivo immunorejection tests while the other, the tumor-specific surface antigen (S antigen, TSSA or MSA) is detected by various in vitro assays, though the relationship of the TSTA to the S antigen is a controversial matter. Adenovirus is also an oncogenic DNA virus and the TSTA has also been demonstrated in adenovirus-induced tumors. But contrary to many reports on SV40-and polyoma virus-tumor systems, only a few papers have been reported on the S antigen. The first reports were those by Hamada and Uetake [4,5] that the appearance of a new virus-specific surface antigen(s) was demonstrated on cells transformed and/or cytocidally infected by adenovirus type 12 (Ad12) by antibody-mediated cytotoxicity and immunofluorescence tests. The second was Costa's report [18] but he described that immunofluorescence staining was observed only when Ad12-induced tumor cells were treated with trypsin, a finding which we have been unable to reconfirm.We have been continuing these lines of research and devised procedures to prepare a highly specific serum for immunofluorescence staining of the S antigen of Ad12-transformed cells.

“…However the relationship between the two antigens is not yet fully established. Of these antigens, the one shown by the FA technique and called surface (S) antigen was readily detectable in Ad 12-transformed cells cultured in vitro (15,21), but not in tumor cells grown in animals unless the cells were treated with a low concentration of trypsin (31). In a previous paper, we described alternate changes of the S antigen on Ad12-transformed cells cultured in vitro and grown in animals (21).…”

mentioning

confidence: 99%

“…In addition, the cytotoxic action of ISC was markedly impeded by pretreating the S(+) cells with antiserum to the S antigen, or the ISC with anti-Thy-1,2 serum plus complement. Taken these findings together, the S(+) cells were assumed to be injured by ISC through direct interaction of the S antigen with T-lymphocytes.In the tumors induced by adenovirus type 12 (Ad12), a virus-specific antigen has been located in their cell surfaces by the in vitro methods of cytotoxicity (2, 5, 17, 27, 28) and of fluorescent antibody (FA) technique (15,21,31), and the in vivo method of immunorejection revealed a virus-specific TSTA (tumor-specific transplantation antigen) (3-7, 11, 12, 18, 22-24, 28-30). However the relationship between the two antigens is not yet fully established.…”

mentioning

confidence: 99%

“…In the tumors induced by adenovirus type 12 (Ad12), a virus-specific antigen has been located in their cell surfaces by the in vitro methods of cytotoxicity (2,5,17,27,28) and of fluorescent antibody (FA) technique (15,21,31), and the in vivo method of immunorejection revealed a virus-specific TSTA (tumor-specific transplantation antigen) (3-7, 11, 12, 18, 22-24, 28-30). However the relationship between the two antigens is not yet fully established.…”

mentioning

confidence: 99%

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Susceptibility of Ad12‐Transformed S (+) and S (‐) Mouse Cells to Cell‐Mediated Immunity In Vitro

Maeta

Microbiology and Immunology

1979

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Adenovirus type 12 (Ad12)-transformed mouse cells were examined for their susceptibility to cell-mediated immunity in vitro, with respect to the activity of the virus-specific surface (S) antigen in the cells. A transformed cell line, C57ATl, was established from embryonic cells of C57BL/6 mice by Ad12 infection. In fluorescent antibody tests, the transformed cells were positive for the S antigen when the cells were maintained as cultures, whereas when the cells were grown as tumors in animals they became negative for the antigen (referred to as S(+) and S(-) cells, respectively). These S(+) and S(-) cells were subjected to the 51Cr-release test for cell lysis by immune spleen cells (ISC) raised in syngeneic mice by Ad12 infection. When the S (+) cells at various passage levels were exposed to ISC, all of them were lysed extensively and to a similar extent irrespective of their passage history. In contrast, the S(-) cells were consistently refractory to the action of ISC. In addition, the cytotoxic action of ISC was markedly impeded by pretreating the S(+) cells with antiserum to the S antigen, or the ISC with anti-Thy-1,2 serum plus complement. Taken these findings together, the S(+) cells were assumed to be injured by ISC through direct interaction of the S antigen with T-lymphocytes.In the tumors induced by adenovirus type 12 (Ad12), a virus-specific antigen has been located in their cell surfaces by the in vitro methods of cytotoxicity (2, 5, 17, 27, 28) and of fluorescent antibody (FA) technique (15,21,31), and the in vivo method of immunorejection revealed a virus-specific TSTA (tumor-specific transplantation antigen) (3-7, 11, 12, 18, 22-24, 28-30). However the relationship between the two antigens is not yet fully established. Of these antigens, the one shown by the FA technique and called surface (S) antigen was readily detectable in Ad 12-transformed cells cultured in vitro (15, 21), but not in tumor cells grown in animals unless the cells were treated with a low concentration of trypsin (31). In a previous paper, we described alternate changes of the S antigen on Ad12-transformed cells cultured in vitro and grown in animals (21). In the FA test, while all of the hamster and mouse cells transformed with Ad12 showed specific and distinct membrane fluorescence, the tumor cells produced by grafting the transformed cells, did not show any fluorescence (referred to as S(+) and S(-) cells, respectively). In the same paper, it was also shown that the S(+) cells were less tumorigenic and more immuno-1085