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In vitro elicitation of cytotoxic response against a nonimmunogenic murine tumor by allosensitization

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Summary

The murine lymphoma (thymoma) PIR-2 of C57BL/6 origin, primarily induced in our laboratory by fractionated X-ray irradiation, has been shown to be nonimmunogenic by its failure to immunize syngeneic mice in vivo or to evoke a cytotoxic response in primary mixed lymphocyte-tumor cell cultures (MLTC) in vitro. We were able, however, to demonstrate the existence of anti-PIR-2 cytotoxic cells among allogeneic-primed C57BL/6 responding lymphocytes using the technique of limiting dilution cultures (LDC). The frequency of anti-PIR-2 cytotoxic cells among C57BL/6 lymphocytes sensitized against BALB/c splenocytes in mixed leukocyte culture (MLC) was 1/20 to 1/40, and the cytotoxic activity of positive LDC wells against PIR-2 reached 60% as determined by a 4-h 51Cr-release assay. The frequency of anti-PIR-2 cytotoxic cells could be increased two- to 10-fold (up to 1/4) by removing nylon-wool-adherent cells from the primed cell population and/or by enriching the primed lymphoblast population on a Percoll density gradient. Anti-PIR-2 cytotoxic cells were found to be Thy1+; Lytl−2+ cells. Clones isolated from the LDC wells manifested strong cytotoxic activity toward PIR-2 cells and the stimulating BALB/c splenocytes but not against other H-2b tumor lines or C57BL/6 splenocytes. We suggest that the procedure of allostimulation in MLC-LDC is an effective in vitro means of generating highly reactive cytotoxic cells against poorly immunogenic neoplasms.

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Authors and Affiliations

  1. The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, 91010, Jerusalem, Israel

    Benny Leshem, Bracha Gotsman & Eli Kedar

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  1. Benny Leshem
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  2. Bracha Gotsman
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  3. Eli Kedar
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Leshem, B., Gotsman, B. & Kedar, E. In vitro elicitation of cytotoxic response against a nonimmunogenic murine tumor by allosensitization. Cancer Immunol Immunother 17, 117–123 (1984). https://doi.org/10.1007/BF00200047

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  • DOI: https://doi.org/10.1007/BF00200047

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