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Studies on the recovery from tolerance to tumor antigens

I. Bone marrow cells from tolerant hosts are not rendered tolerant, but provide potential to reconstitute tumor-specific effector T cell clones

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Summary

The present study investigates the potential of bone marrow cells from mice tolerant to tumor antigens to repopulate tumor-specific effector T cells. C3H/He mice were inoculated i.v. with 106 10000 R X-irradiated syngeneic X5563 plasmacytoma tumor cells three times at 4-day intervals. This regimen abrogated the ability of spleen cells from these mice to develop anti-X5563 cytotoxic and in vivo protective (tumor-neutralizing) T cell-mediated immunity as induced by i.d. inoculation of viable X5563 cells followed by surgical resection of the tumor. Since such suppression was induced in a tumor-specific way, this represented a state of antitumor tolerance. When bone marrow cells from normal or X5563-tolerant mice were transferred i.v. into 950 R X-irradiated syngeneic C3H/He mice, both groups of recipient mice generated anti-X5563 tumor immunity over a similar time course and to almost the same degree. Anti-X5563 tumor immunity induced in (C3H/He×C57BL/6) F1 mice which had been transferred with bone marrow cells from normal or X5563-tolerant C3H/He mice were mediated by T cells expressing the Ly phenotype of C3H/He, but not of C57BL/6, excluding the possibility that the antitumor effector cells were derived from recipient mice. It was also demonstrated that C3H/He mice which had been reconstituted with normal marrow were rendered tolerant when the tolerance regimen was started 7 weeks, but not 1 week after the bone marrow reconstitution. These results indicate that bone marrow cells from antitumor tolerant mice are not rendered tolerant to the tumor but can provide the potential to repopulate antitumor CTL and in vivo protective effector T cells.

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Authors and Affiliations

  1. From the Department of Oncogenesis, Institute for Cancer Research, Osaka University Medical School, 1-1-50, Fukushima, Fukushima-ku, 553, Osaka, Japan

    Hiromi Fujiwara, Soichiro Sato, Atsushi Kosugi, Masahiro Fukuzawa & Toshiyuki Hamaoka

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  1. Hiromi Fujiwara
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  2. Soichiro Sato
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  3. Atsushi Kosugi
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  4. Masahiro Fukuzawa
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  5. Toshiyuki Hamaoka
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This work was supported by the Special Project Cancer-Bioscience from the Ministry of Education, Science and Culture, Japan

Abbreviations used: MHC, major histocompatibility complex; CTL, cytotoxic T lymphocytes; TNP, trinitrophenyl; C, complement; TNBS; trinitrobenzene sulfonate; MMC, mitomycin C

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Fujiwara, H., Sato, S., Kosugi, A. et al. Studies on the recovery from tolerance to tumor antigens. Cancer Immunol Immunother 24, 113–120 (1987). https://doi.org/10.1007/BF00205587

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  • DOI: https://doi.org/10.1007/BF00205587

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