Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Jun 1;165(6):1624–1638. doi: 10.1084/jem.165.6.1624

Early genetic events in T cell development analyzed by in situ hybridization

PMCID: PMC2188376  PMID: 2884272

Abstract

In situ hybridization was used to investigate the expression of T cell receptor (TCR) alpha, beta, and gamma mRNAs in developing fetal and adult precursor thymocytes. gamma transcription was observed at the earliest time tested (day 12), followed by beta 12 h later, and TCR alpha on day 16. The early beta transcripts appeared to be from unrearranged or incompletely rearranged (D-J-C) beta loci. V beta region transcription was first detectable on day 14 and transcription of different V beta genes was induced at different times. These results delineate a schedule sequence of TCR gene activation, which begins within 1 d after entry of stem cells into the fetal thymus.

Full Text

The Full Text of this article is available as a PDF (861.4 KB).

Selected References

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

  1. 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]
  2. Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Born W., Yagüe J., Palmer E., Kappler J., Marrack P. Rearrangement of T-cell receptor beta-chain genes during T-cell development. Proc Natl Acad Sci U S A. 1985 May;82(9):2925–2929. doi: 10.1073/pnas.82.9.2925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ceredig R., Dialynas D. P., Fitch F. W., MacDonald H. R. Precursors of T cell growth factor producing cells in the thymus: ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5. J Exp Med. 1983 Nov 1;158(5):1654–1671. doi: 10.1084/jem.158.5.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
  7. Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
  8. Fowlkes B. J., Edison L., Mathieson B. J., Chused T. M. Early T lymphocytes. Differentiation in vivo of adult intrathymic precursor cells. J Exp Med. 1985 Sep 1;162(3):802–822. doi: 10.1084/jem.162.3.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fox D. A., Hussey R. E., Fitzgerald K. A., Bensussan A., Daley J. F., Schlossman S. F., Reinherz E. L. Activation of human thymocytes via the 50KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptors on both T3+ and T3- populations. J Immunol. 1985 Jan;134(1):330–335. [PubMed] [Google Scholar]
  10. Furley A. J., Mizutani S., Weilbaecher K., Dhaliwal H. S., Ford A. M., Chan L. C., Molgaard H. V., Toyonaga B., Mak T., van den Elsen P. Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex. Cell. 1986 Jul 4;46(1):75–87. doi: 10.1016/0092-8674(86)90861-5. [DOI] [PubMed] [Google Scholar]
  11. Gunter K. C., Kroczek R. A., Shevach E. M., Germain R. N. Functional expression of the murine Thy-1.2 gene in transfected human T cells. J Exp Med. 1986 Feb 1;163(2):285–300. doi: 10.1084/jem.163.2.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gunter K. C., Malek T. R., Shevach E. M. T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4. J Exp Med. 1984 Mar 1;159(3):716–730. doi: 10.1084/jem.159.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Iwamoto A., Rupp F., Ohashi P. S., Walker C. L., Pircher H., Joho R., Hengartner H., Mak T. W. T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J Exp Med. 1986 May 1;163(5):1203–1212. doi: 10.1084/jem.163.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kaye J., Porcelli S., Tite J., Jones B., Janeway C. A., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. doi: 10.1084/jem.158.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mathieson B. J., Sharrow S. O., Rosenberg Y., Hämmerling U. Lyt 1+23- cells appear in the thymus before Lyt 123+ cells. Nature. 1981 Jan 15;289(5794):179–181. doi: 10.1038/289179a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Moore M. A., Owen J. J. Experimental studies on the development of the thymus. J Exp Med. 1967 Oct 1;126(4):715–726. doi: 10.1084/jem.126.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nelson K. J., Kelley D. E., Perry R. P. Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5305–5309. doi: 10.1073/pnas.82.16.5305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Norcross M. A., Smith R. T. Regulation of T cell mitogen activity of anti-lymphocyte serum by a B-helper cell. J Immunol. 1979 Apr;122(4):1620–1628. [PubMed] [Google Scholar]
  24. Owen J. J., Raff M. C. Studies on the differentiation of thymus-derived lymphocytes. J Exp Med. 1970 Dec 1;132(6):1216–1232. doi: 10.1084/jem.132.6.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Owen J. J., Ritter M. A. Tissue interaction in the development of thymus lymphocytes. J Exp Med. 1969 Feb 1;129(2):431–442. doi: 10.1084/jem.129.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Roehm N., Herron L., Cambier J., DiGuisto D., Haskins K., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells: distribution on thymus and peripheral T cells. Cell. 1984 Sep;38(2):577–584. doi: 10.1016/0092-8674(84)90512-9. [DOI] [PubMed] [Google Scholar]
  28. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
  29. Saito T., Weiss A., Miller J., Norcross M. A., Germain R. N. Specific antigen-Ia activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes. Nature. 1987 Jan 8;325(7000):125–130. doi: 10.1038/325125a0. [DOI] [PubMed] [Google Scholar]
  30. Samelson L. E., Germain R. N., Schwartz R. H. Monoclonal antibodies against the antigen receptor on a cloned T-cell hybrid. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6972–6976. doi: 10.1073/pnas.80.22.6972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Snodgrass H. R., Kisielow P., Kiefer M., Steinmetz M., von Boehmer H. Ontogeny of the T-cell antigen receptor within the thymus. Nature. 1985 Feb 14;313(6003):592–595. doi: 10.1038/313592a0. [DOI] [PubMed] [Google Scholar]
  34. Van Ewijk W., Jenkinson E. J., Owen J. J. Detection of Thy-1, T-200, Lyt-1 and Lyt-2-bearing cells in the developing lymphoid organs of the mouse embryo in vivo and in vitro. Eur J Immunol. 1982 Apr;12(4):262–271. doi: 10.1002/eji.1830120403. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [DOI] [PubMed] [Google Scholar]
  37. Yancopoulos G. D., Desiderio S. V., Paskind M., Kearney J. F., Baltimore D., Alt F. W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature. 1984 Oct 25;311(5988):727–733. doi: 10.1038/311727a0. [DOI] [PubMed] [Google Scholar]
  38. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. von Boehmer H., Crisanti A., Kisielow P., Haas W. Absence of growth by most receptor-expressing fetal thymocytes in the presence of interleukin-2. Nature. 1985 Apr 11;314(6011):539–540. doi: 10.1038/314539a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES