In vitro generation of cytotoxic lymphocytes against radiation and radiation leukemia virus-induced tumors

Yefenof, Eitan; Tchakirov, Rachel; Kedar, Eli

doi:10.1007/bf00205669

Cited by 14 publications

(26 citation statements)

References 42 publications

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“…The more notable successes have been achieved with tumor lines that had been chemically or virally induced and repeatedly passaged; other lines failed to elicit a cytotoxic response and are hence defined as nonimmunogenic [14,29].…”

Section: Discussionmentioning

confidence: 98%

“…To avoid prolonged maintenance in vitro, new frozen aliquots of the lymphoma cells were thawed every 6 -8 weeks. The lymphoma line PIR-2 was shown by repeated examinations to be gp70-negative [29]. Other tumor cell lines used were: Madison 109 (M109), a spontaneous lung carcinoma of BALB/c mice; YAC, a Moloney virus-induced lymphoma of A mice; RBL-5, a Rauscher virus-induced lymphoma of C57BL/6 mice; and 136.5 and 127, radiation leukemia virus (RadLV)-induced lymphomas of C57BL/6 mice.…”

Section: Methodsmentioning

confidence: 99%

“…PIR-2 thymoma was induced in our laboratory as described elsewhere [29]. Briefly, adult C57BL/6 mice were exposed weekly to fractionated (4 x 170 R) X-irradiation.…”

Section: Methodsmentioning

confidence: 99%

“…It has been shown to be nonimmunogenic by its failure to evoke transplantation immunity in syngeneic mice in vivo and to elicit a cytotoxic response in MLTC in vitro [29]. Moreover, PIR-2 cells, like several other radiation-induced lymphoma cells, do not express membrane-associated virion antigens [12,19,29].…”

Section: Introductionmentioning

confidence: 98%

“…Offprint requests to: B. Leshem months after X-irradiation (4 x 170 R) [29]. It has been shown to be nonimmunogenic by its failure to evoke transplantation immunity in syngeneic mice in vivo and to elicit a cytotoxic response in MLTC in vitro [29].…”

Section: Introductionmentioning

confidence: 99%

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

Leshem

Gotsman

Kedar

1984

Cancer Immunol Immunother

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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+; Lyt1-2+ 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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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

“…PIR-2 thymoma was induced in our laboratory as described elsewhere [29]. Briefly, adult C57BL/6 mice were exposed weekly to fractionated (4 x 170 R) X-irradiation.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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

Leshem

Gotsman

Kedar

1984

Cancer Immunol Immunother

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High‐ and low‐leukemogenic variants of the radiation leukemia virus (RadLV) differ in ability to induce tumor‐specific immune suppression

Yefenof¹,

Zilcha²

1982

Intl Journal of Cancer

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Adult C57BL/6 mice inoculated intrathymically (i.t.) with the highly leukemogenic variant of the radiation leukemia virus (A-RadLV) develop suppressor cells capable of specifically abrogating a potential anti-tumor cytotoxic response in vitro. Suppressor cells were generated directly by the virus, independently of an initiation of a leukemogenic process. Inoculation of C57BL/6 animals with the low leukemogenic D-RadLV variant did not result in suppressor cell generation. It is proposed that induction of tumor-specific immune suppression by A-RadLV is essential for tumor progression, and the leukemogenic activity of D-RadLV is attributed to its inability to recruit suppressor cells.

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High‐ and low‐leukemogenic variants of the radiation leukemia virus (RadLV): Immunogenic, suppressive and genetic properties in relation to leukemogenic activity

Yefenof¹,

David²,

Kotler

1984

Intl Journal of Cancer

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C57BL/6 (B6) mice inoculated with the highly leukemogenic variant of the radiation leukemia virus (A-RadLV) develop suppressor cells capable of abrogating potential anti-tumor immunity in vitro and in vivo. Inoculation of B6 animals with the low-leukemogenic D-RadLV variant does not result in suppressor cell generation but induces antitumor reactive lymphocytes. A-RadLV and D-RadLV are not leukemogenic in BALB/c or (B6 X BALB/c)F1(F1) mice, and reactive but not suppressor lymphocytes could be demonstrated in F1 animals inoculated with either virus. Infectivity assays and fingerprint analysis revealed that A-RadLV and D-RadLV contain viruses with N and B tropism. In addition, thymoma cells induced by A-RadLV produced another virus with a fingerprint pattern containing X-MuLV elements. The possible implications of the different virus types on the immunogenic and leukemogenic properties of the RadLV variants are discussed.

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In vitro generation of cytotoxic lymphocytes against radiation and radiation leukemia virus-induced tumors

Cited by 14 publications

References 42 publications

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

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

High‐ and low‐leukemogenic variants of the radiation leukemia virus (RadLV) differ in ability to induce tumor‐specific immune suppression

High‐ and low‐leukemogenic variants of the radiation leukemia virus (RadLV): Immunogenic, suppressive and genetic properties in relation to leukemogenic activity

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