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. 1988 Aug;56(8):2069–2074. doi: 10.1128/iai.56.8.2069-2074.1988

Age-associated increase in the expression of T-cell antigen receptor gamma-chain gene in conventional and germfree mice.

Y Yoshikai 1, G Matsuzaki 1, K Kishihara 1, K Nomoto 1, T Yokokura 1, K Nomoto 1
PMCID: PMC259524  PMID: 2969376

Abstract

To determine whether environmental antigens such as intestinal microflora contribute to expansion of the T-cell repertoire, age-related changes in the expression level of T-cell antigen receptor genes encoding gamma, beta, and alpha chains were compared in the lymphoid tissues of conventional versus germfree mice. Irrespective of the conditions of maintenance, an age-associated increase in the expression of the gamma-chain gene was evident in the thymus and spleen. Both conventional and germfree old mice (age, 40 weeks) had a relatively high proportion of Thy1+ L3T4- Lyt2- cells but a reduced level of Thy1+ L3T4- Lyt2+ cells in the thymus compared with their counterparts (age 8 weeks). The thymic dysfunction but not the stimulation by intestinal microflora may contribute to this age-related increase in gamma-gene transcripts in these tissues. On the other hand, an age-associated increase in the expression of gamma RNA was not evident in the mesenteric lymph nodes of germfree mice, although a remarkable increase in the gamma-chain gene messages was detected in the lymph nodes of the aged conventional mice. These results suggest that the expression of gamma RNA in cells of gut-associated lymphoid tissue is partly influenced by intestinal microflora.

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Selected References

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

  1. Adkins B., Mueller C., Okada C. Y., Reichert R. A., Weissman I. L., Spangrude G. J. Early events in T-cell maturation. Annu Rev Immunol. 1987;5:325–365. doi: 10.1146/annurev.iy.05.040187.001545. [DOI] [PubMed] [Google Scholar]
  2. Allison J. P., McIntyre B. W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982 Nov;129(5):2293–2300. [PubMed] [Google Scholar]
  3. Band H., Hochstenbach F., McLean J., Hata S., Krangel M. S., Brenner M. B. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–684. doi: 10.1126/science.3672118. [DOI] [PubMed] [Google Scholar]
  4. Bank I., DePinho R. A., Brenner M. B., Cassimeris J., Alt F. W., Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986 Jul 10;322(6075):179–181. doi: 10.1038/322179a0. [DOI] [PubMed] [Google Scholar]
  5. Bonyhadi M., Weiss A., Tucker P. W., Tigelaar R. E., Allison J. P. Delta is the Cx-gene product in the gamma/delta antigen receptor of dendritic epidermal cells. Nature. 1987 Dec 10;330(6148):574–576. doi: 10.1038/330574a0. [DOI] [PubMed] [Google Scholar]
  6. Born W., Miles C., White J., O'Brien R., Freed J. H., Marrack P., Kappler J., Kubo R. T. Peptide sequences of T-cell receptor delta and gamma chains are identical to predicted X and gamma proteins. Nature. 1987 Dec 10;330(6148):572–574. doi: 10.1038/330572a0. [DOI] [PubMed] [Google Scholar]
  7. Born W., Rathbun G., Tucker P., Marrack P., Kappler J. Synchronized rearrangement of T-cell gamma and beta chain genes in fetal thymocyte development. Science. 1986 Oct 24;234(4775):479–482. doi: 10.1126/science.3020688. [DOI] [PubMed] [Google Scholar]
  8. Borst J., van de Griend R. J., van Oostveen J. W., Ang S. L., Melief C. J., Seidman J. G., Bolhuis R. L. A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. Nature. 1987 Feb 19;325(6106):683–688. doi: 10.1038/325683a0. [DOI] [PubMed] [Google Scholar]
  9. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  10. Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
  11. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  12. Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
  13. Chien Y., Becker D. M., Lindsten T., Okamura M., Cohen D. I., Davis M. M. A third type of murine T-cell receptor gene. Nature. 1984 Nov 1;312(5989):31–35. doi: 10.1038/312031a0. [DOI] [PubMed] [Google Scholar]
  14. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  15. Ernst D. N., Weigle W. O., Thoman M. L. Retention of T cell reactivity to mitogens and alloantigens by Peyer's patch cells of aged mice. J Immunol. 1987 Jan 1;138(1):26–31. [PubMed] [Google Scholar]
  16. Haars R., Kronenberg M., Gallatin W. M., Weissman I. L., Owen F. L., Hood L. Rearrangement and expression of T cell antigen receptor and gamma genes during thymic development. J Exp Med. 1986 Jul 1;164(1):1–24. doi: 10.1084/jem.164.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haskins K., Kubo R., White J., Pigeon M., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983 Apr 1;157(4):1149–1169. doi: 10.1084/jem.157.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hata S., Brenner M. B., Krangel M. S. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–682. doi: 10.1126/science.3499667. [DOI] [PubMed] [Google Scholar]
  19. Hayday A. C., Diamond D. J., Tanigawa G., Heilig J. S., Folsom V., Saito H., Tonegawa S. Unusual organization and diversity of T-cell receptor alpha-chain genes. 1985 Aug 29-Sep 4Nature. 316(6031):828–832. doi: 10.1038/316828a0. [DOI] [PubMed] [Google Scholar]
  20. Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
  21. Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
  22. Hooijkaas H., Benner R., Pleasants J. R., Wostmann B. S. Isotypes and specificities of immunoglobulins produced by germ-free mice fed chemically defined ultrafiltered "antigen-free" diet. Eur J Immunol. 1984 Dec;14(12):1127–1130. doi: 10.1002/eji.1830141212. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Kishihara K., Yoshikai Y., Matsuzaki G., Mak T. W., Nomoto K. Functional alpha and beta T cell chain receptor messages can be detected in old but not in young athymic mice. Eur J Immunol. 1987 Apr;17(4):477–482. doi: 10.1002/eji.1830170407. [DOI] [PubMed] [Google Scholar]
  25. Loh E. Y., Lanier L. L., Turck C. W., Littman D. R., Davis M. M., Chien Y. H., Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature. 1987 Dec 10;330(6148):569–572. doi: 10.1038/330569a0. [DOI] [PubMed] [Google Scholar]
  26. Makinodan T., Kay M. M. Age influence on the immune system. Adv Immunol. 1980;29:287–330. doi: 10.1016/s0065-2776(08)60047-4. [DOI] [PubMed] [Google Scholar]
  27. Matsuzaki G., Yoshikai Y., Kishihara K., Nomoto K. Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation. J Immunol. 1988 Jan 15;140(2):384–387. [PubMed] [Google Scholar]
  28. Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Schlossman S. F., Reinherz E. L. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nakanishi N., Maeda K., Ito K., Heller M., Tonegawa S. T gamma protein is expressed on murine fetal thymocytes as a disulphide-linked heterodimer. Nature. 1987 Feb 19;325(6106):720–723. doi: 10.1038/325720a0. [DOI] [PubMed] [Google Scholar]
  30. Pardoll D. M., Fowlkes B. J., Lechler R. I., Germain R. N., Schwartz R. H. Early genetic events in T cell development analyzed by in situ hybridization. J Exp Med. 1987 Jun 1;165(6):1624–1638. doi: 10.1084/jem.165.6.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Raulet D. H., Garman R. D., Saito H., Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. doi: 10.1038/314103a0. [DOI] [PubMed] [Google Scholar]
  32. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  33. Samelson L. E., Lindsten T., Fowlkes B. J., van den Elsen P., Terhorst C., Davis M. M., Germain R. N., Schwartz R. H. Expression of genes of the T-cell antigen receptor complex in precursor thymocytes. 1985 Jun 27-Jul 3Nature. 315(6022):765–768. doi: 10.1038/315765a0. [DOI] [PubMed] [Google Scholar]
  34. Scollay R. Thymus cell migration: cells migrating from thymus to peripheral lymphoid organs have a "mature" phenotype. J Immunol. 1982 Apr;128(4):1566–1570. [PubMed] [Google Scholar]
  35. Snodgrass H. R., Dembić Z., Steinmetz M., von Boehmer H. Expression of T-cell antigen receptor genes during fetal development in the thymus. Nature. 1985 May 16;315(6016):232–233. doi: 10.1038/315232a0. [DOI] [PubMed] [Google Scholar]
  36. Toyonaga B., Yoshikai Y., Vadasz V., Chin B., Mak T. W. Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8624–8628. doi: 10.1073/pnas.82.24.8624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weissman I. L. Thymus cell migration. J Exp Med. 1967 Aug 1;126(2):291–304. doi: 10.1084/jem.126.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Winoto A., Mjolsness S., Hood L. Genomic organization of the genes encoding mouse T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):832–836. doi: 10.1038/316832a0. [DOI] [PubMed] [Google Scholar]
  39. Yanagi Y., Yoshikai Y., Leggett K., Clark S. P., Aleksander I., Mak T. W. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984 Mar 8;308(5955):145–149. doi: 10.1038/308145a0. [DOI] [PubMed] [Google Scholar]
  40. Yoshikai Y., Clark S. P., Taylor S., Sohn U., Wilson B. I., Minden M. D., Mak T. W. Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):837–840. doi: 10.1038/316837a0. [DOI] [PubMed] [Google Scholar]
  41. Yoshikai Y., Reis M. D., Mak T. W. Athymic mice express a high level of functional gamma-chain but greatly reduced levels of alpha- and beta-chain T-cell receptor messages. Nature. 1986 Dec 4;324(6096):482–485. doi: 10.1038/324482a0. [DOI] [PubMed] [Google Scholar]

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