Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Apr;83(8):2488–2491. doi: 10.1073/pnas.83.8.2488

Frequency of 6-thioguanine-resistant T cells is inversely related to the declining T-cell activities in aging mice.

T Inamizu, N Kinohara, M P Chang, T Makinodan
PMCID: PMC323323  PMID: 3486421

Abstract

The frequency of clonable 6-thioguanine-resistant (6-TGr) splenic T cells increased moderately with age in female BALB/c mice ranging in age from 3 to 32 months; however, the correlation between the frequency of clonable 6-TGr cells and age was weak. Those clonable 6-TGr T cells were deficient in hypoxanthine/guanine phosphoribosyltransferase (HGPRT) activity and sensitive to hypoxanthine/aminopterin/thymidine medium, as in the case of HGPRT-deficient L5178Y mouse lymphoma cells. When splenic T cells of individual aging mice were assessed simultaneously for the frequency of clonable 6-TGr T cells and for their ability to produce interleukin 2 or to proliferate in response to mitogenic stimulation, an inverse correlation was observed. These results indicate that the frequency of 6-TGr T cells is more closely related to physiologic age than chronologic age. This would mean that the frequency could be used as an index of physiologic age and that the T cells could serve as a cellular model relating gene alterations to physiologic age.

Full text

PDF
2488

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albertini R. J., Castle K. L., Borcherding W. R. T-cell cloning to detect the mutant 6-thioguanine-resistant lymphocytes present in human peripheral blood. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6617–6621. doi: 10.1073/pnas.79.21.6617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albertini R. J., DeMars R. Somatic cell mutation. Detection and quantification of x-ray-induced mutation in cultured, diploid human fibroblasts. Mutat Res. 1973 May;18(2):199–224. doi: 10.1016/0027-5107(73)90037-7. [DOI] [PubMed] [Google Scholar]
  3. Albertini R. J., O'Neill J. P., Nicklas J. A., Heintz N. H., Kelleher P. C. Alterations of the hprt gene in human in vivo-derived 6-thioguanine-resistant T lymphocytes. Nature. 1985 Jul 25;316(6026):369–371. doi: 10.1038/316369a0. [DOI] [PubMed] [Google Scholar]
  4. Albertini R. J. Somatic gene mutations in vivo as indicated by the 6-thioguanine-resistant T-lymphocytes in human blood. Mutat Res. 1985 Jun-Jul;150(1-2):411–422. doi: 10.1016/0027-5107(85)90138-1. [DOI] [PubMed] [Google Scholar]
  5. Andersson J., Grönvik K. O., Larsson E. L., Coutinho A. Studies on T lymphocyte activation. I. Requirements for the mitogen-dependent production of T cell growth factors. Eur J Immunol. 1979 Aug;9(8):581–587. doi: 10.1002/eji.1830090802. [DOI] [PubMed] [Google Scholar]
  6. Chang M. P., Makinodan T., Peterson W. J., Strehler B. L. Role of T cells and adherent cells in age-related decline in murine interleukin 2 production. J Immunol. 1982 Dec;129(6):2426–2430. [PubMed] [Google Scholar]
  7. DeMars R., Held K. R. The spontaneous azaguanine-resistant mutants of diploid human fibroblasts. Humangenetik. 1972;16(1):87–110. doi: 10.1007/BF00393992. [DOI] [PubMed] [Google Scholar]
  8. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  9. Goldstein S., Shmookler Reis R. J. Genetic modifications during cellular aging. Mol Cell Biochem. 1984 Sep;64(1):15–30. doi: 10.1007/BF00420924. [DOI] [PubMed] [Google Scholar]
  10. Greiner D. L., Goldschneider I., Barton R. W. Identification of thymocyte progenitors in hemopoietic tissues of the rat. II. Enrichment of functional prothymocytes on the fluorescence-activated cell sorter. J Exp Med. 1982 Nov 1;156(5):1448–1460. doi: 10.1084/jem.156.5.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hart R. W., Setlow R. B. Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2169–2173. doi: 10.1073/pnas.71.6.2169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horn P. L., Turker M. S., Ogburn C. E., Disteche C. M., Martin G. M. A cloning assay for 6-thioguanine resistance provides evidence against certain somatic mutational theories of aging. J Cell Physiol. 1984 Nov;121(2):309–315. doi: 10.1002/jcp.1041210207. [DOI] [PubMed] [Google Scholar]
  13. JACOBS P. A., COURT BROWN W. M., DOLL R. Distribution of human chromosome counts in relation to age. Nature. 1961 Sep 16;191:1178–1180. doi: 10.1038/1911178a0. [DOI] [PubMed] [Google Scholar]
  14. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  15. Norman A., Cochran S., Bass D., Roe D. Effects of age, sex and diagnostic X-rays on chromosome damage. Int J Radiat Biol Relat Stud Phys Chem Med. 1984 Sep;46(3):317–321. doi: 10.1080/09553008414551451. [DOI] [PubMed] [Google Scholar]
  16. Price G. B., Makinodan T. Immunologic deficiencies in senescence. I. Characterization of intrinsic deficiencies. J Immunol. 1972 Feb;108(2):403–412. [PubMed] [Google Scholar]
  17. Scollay R., Shortman K. Thymocyte subpopulations: an experimental review, including flow cytometric cross-correlations between the major murine thymocyte markers. Thymus. 1983 Sep;5(5-6):245–295. [PubMed] [Google Scholar]
  18. Siminovitch L. On the nature of hereditable variation in cultured somatic cells. Cell. 1976 Jan;7(1):1–11. doi: 10.1016/0092-8674(76)90249-x. [DOI] [PubMed] [Google Scholar]
  19. Stutman O. Intrathymic and extrathymic T cell maturation. Immunol Rev. 1978;42:138–184. doi: 10.1111/j.1600-065x.1978.tb00261.x. [DOI] [PubMed] [Google Scholar]
  20. Trainor K. J., Wigmore D. J., Chrysostomou A., Dempsey J. L., Seshadri R., Morley A. A. Mutation frequency in human lymphocytes increases with age. Mech Ageing Dev. 1984 Sep;27(1):83–86. doi: 10.1016/0047-6374(84)90084-8. [DOI] [PubMed] [Google Scholar]
  21. Turner D. R., Morley A. A., Haliandros M., Kutlaca R., Sanderson B. J. In vivo somatic mutations in human lymphocytes frequently result from major gene alterations. Nature. 1985 May 23;315(6017):343–345. doi: 10.1038/315343a0. [DOI] [PubMed] [Google Scholar]
  22. Vijayalaxmi, Evans H. J. Measurement of spontaneous and X-irradiation-induced 6-thioguanine-resistant human blood lymphocytes using a T-cell cloning technique. Mutat Res. 1984 Jan;125(1):87–94. doi: 10.1016/0027-5107(84)90035-6. [DOI] [PubMed] [Google Scholar]
  23. Yamagishi H., Kunisada T., Takeda T. Amplification of extrachromosomal small circular DNAs in a murine model of accelerated senescence. A brief note. Mech Ageing Dev. 1985 Jan;29(1):101–103. doi: 10.1016/0047-6374(85)90051-x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES