Cyclical changes in susceptibility of a myeloma tumor (LPC-1) to immune destruction. II. Periodic fluctuations during growth in normal and nude mice and in culture

A. H. Hale, Esteban Celis, J. H. Russell, H. N. Eisen

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Abstract

Cells of the LPC-1 myeloma tumor (of BALB/c origin) were tested periodically for susceptibility to lysis by anti-H-2 cytotoxic T lymphocytes (CTL) and by complement-dependent anti-H-2 antibodies (Ab), and for ability to adsorb these Ab, as the cells grew in culture and in ascites form in nude (BALB/c x nu) and in normal BALB/c mice. Cells harvested from 2 to 8 days after inoculation into the peritoneal cavity had the 'early' phenotype: they were extensively lysed by the CTL and Ab and effectively adsorbed the Ab. Cells harvested on day 8 and afterward had the 'late' phenotype: they were not lysed by CTL, required more Ab for lysis, and had about 8-fold less ability (per cell) to adsorb the Ab. All of these activities were completely reversed 2 to 4 days after transferring late cells into fresh BALB/c hosts. LPC-1 cells growing in nude BALB/c mice also changed from the early, CTL-susceptible to the late CTL-resistant phenotype. With repeated cell counts and measurements of 125I-iododeoxiuridine incorporation to estimate growth, it was found that exponentially growing cells had the early phenotype and that cells in stationary phase had the late phenotype. When placed in culture, the early cells retained their phenotype indefinitely (up to 40 days). However, the late cells switched phenotype: initially resistant to CTL and Ab, after 1 to 4 days in culture they became fully susceptible to CTL and highly reactive with the Ab, and these features persisted in culture thereafter. This transition occurred even when the late, resistant cells were prevented from dividing in culture by prior irradiation (10,000 R) or by trinitrophenylation with 2,4,6-trinitrobenzenesulfonic acid. The findings in both nude mice and in culture indicate that the reversible, early-late phenotype changes are due to changes in individual cells, rather than to immunoselection of preexisting variant cells.

Original languageEnglish (US)
Pages (from-to)959-964
Number of pages6
JournalJournal of Immunology
Volume122
Issue number3
StatePublished - Dec 1 1979
Externally publishedYes

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Nude Mice
Cytotoxic T-Lymphocytes
Growth
Neoplasms
Phenotype
Antibodies
Trinitrobenzenesulfonic Acid
Peritoneal Cavity
Ascites
Cell Culture Techniques
Cell Count

ASJC Scopus subject areas

  • Immunology

Cite this

Cyclical changes in susceptibility of a myeloma tumor (LPC-1) to immune destruction. II. Periodic fluctuations during growth in normal and nude mice and in culture. / Hale, A. H.; Celis, Esteban; Russell, J. H.; Eisen, H. N.

In: Journal of Immunology, Vol. 122, No. 3, 01.12.1979, p. 959-964.

Research output: Contribution to journalArticle

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abstract = "Cells of the LPC-1 myeloma tumor (of BALB/c origin) were tested periodically for susceptibility to lysis by anti-H-2 cytotoxic T lymphocytes (CTL) and by complement-dependent anti-H-2 antibodies (Ab), and for ability to adsorb these Ab, as the cells grew in culture and in ascites form in nude (BALB/c x nu) and in normal BALB/c mice. Cells harvested from 2 to 8 days after inoculation into the peritoneal cavity had the 'early' phenotype: they were extensively lysed by the CTL and Ab and effectively adsorbed the Ab. Cells harvested on day 8 and afterward had the 'late' phenotype: they were not lysed by CTL, required more Ab for lysis, and had about 8-fold less ability (per cell) to adsorb the Ab. All of these activities were completely reversed 2 to 4 days after transferring late cells into fresh BALB/c hosts. LPC-1 cells growing in nude BALB/c mice also changed from the early, CTL-susceptible to the late CTL-resistant phenotype. With repeated cell counts and measurements of 125I-iododeoxiuridine incorporation to estimate growth, it was found that exponentially growing cells had the early phenotype and that cells in stationary phase had the late phenotype. When placed in culture, the early cells retained their phenotype indefinitely (up to 40 days). However, the late cells switched phenotype: initially resistant to CTL and Ab, after 1 to 4 days in culture they became fully susceptible to CTL and highly reactive with the Ab, and these features persisted in culture thereafter. This transition occurred even when the late, resistant cells were prevented from dividing in culture by prior irradiation (10,000 R) or by trinitrophenylation with 2,4,6-trinitrobenzenesulfonic acid. The findings in both nude mice and in culture indicate that the reversible, early-late phenotype changes are due to changes in individual cells, rather than to immunoselection of preexisting variant cells.",
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