Skip to main content
Immunology logoLink to Immunology
. 1991 Jan;72(1):20–26.

Two differential pathways from double-negative to double-positive thymocytes.

K Matsumoto 1, Y Yoshikai 1, Y Moroi 1, T Asano 1, T Ando 1, K Nomoto 1
PMCID: PMC1384330  PMID: 1825481

Abstract

Murine thymocytes are divided into four major populations on the basis of expression of CD4 and CD8 antigens. The bulk of evidence favours the view that CD4-CD8- cells can develop into CD4-CD8+ and CD4+CD8- cells via the CD4+CD8+ stage in the thymus. However, CD4-CD8+ and CD4+CD8- thymocyte subsets contain not only CD3+ mature cells but also CD3- immature cells, which seem to be intermediate cells between CD4-CD8- and CD4+CD8+ cells. Here we demonstrate mouse strain differences in the proportion of immature single-positive thymocyte subsets in thymus at the steady or developing state. In C3H mice, immature CD4+CD8- is dominant in proportion over CD4-CD8+ in foetal thymus and in donor-derived thymocytes at an early stage of bone marrow transplantation. On the other hand, immature CD4-CD8+ is dominant over CD4+CD8- during T-cell development in the case of B10.BR mice. An intermediate pattern was shown in the case of F1 mice. Both of these immature single-positive subsets gave rise to double-positive cells after 24 hr culture. These results suggest that there exist two distinct differential pathways; one is from CD4-CD8- cells to CD4+CD8+ cells via CD4-CD8+ cells, and another is via CD4+CD8- cells, and that an application of the 'CD8 pathway' or 'CD4 pathway' seems to be genetically destined by BM-derived cells but not by thymic stromal cells.

Full text

PDF
21

Selected References

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

  1. Bluestone J. A., Pardoll D., Sharrow S. O., Fowlkes B. J. Characterization of murine thymocytes with CD3-associated T-cell receptor structures. Nature. 1987 Mar 5;326(6108):82–84. doi: 10.1038/326082a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Ceredig R. Differentiation potential of 14-day fetal mouse thymocytes in organ culture. Analysis of CD4/CD8-defined single-positive and double-negative cells. J Immunol. 1988 Jul 15;141(2):355–362. [PubMed] [Google Scholar]
  4. Crispe I. N., Bevan M. J. Expression and functional significance of the J11d marker on mouse thymocytes. J Immunol. 1987 Apr 1;138(7):2013–2018. [PubMed] [Google Scholar]
  5. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  6. 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]
  7. Fowlkes B. J., Pardoll D. M. Molecular and cellular events of T cell development. Adv Immunol. 1989;44:207–264. doi: 10.1016/s0065-2776(08)60643-4. [DOI] [PubMed] [Google Scholar]
  8. Fowlkes B. J., Schwartz R. H., Pardoll D. M. Deletion of self-reactive thymocytes occurs at a CD4+8+ precursor stage. Nature. 1988 Aug 18;334(6183):620–623. doi: 10.1038/334620a0. [DOI] [PubMed] [Google Scholar]
  9. Guidos C. J., Weissman I. L., Adkins B. Intrathymic maturation of murine T lymphocytes from CD8+ precursors. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7542–7546. doi: 10.1073/pnas.86.19.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Havran W. L., Poenie M., Kimura J., Tsien R., Weiss A., Allison J. P. Expression and function of the CD3-antigen receptor on murine CD4+8+ thymocytes. Nature. 1987 Nov 12;330(6144):170–173. doi: 10.1038/330170a0. [DOI] [PubMed] [Google Scholar]
  11. Hirokawa K., Sado T., Kubo S., Kamisaku H., Hitomi K., Utsuyama M. Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study. J Immunol. 1985 Jun;134(6):3615–3624. [PubMed] [Google Scholar]
  12. Hugo P., Waanders G. A., Scollay R., Shortman K., Boyd R. L. Ontogeny of a novel CD4+CD8-CD3- thymocyte subpopulation: a comparison with CD4- CD8+ CD3- thymocytes. Int Immunol. 1990;2(3):209–218. doi: 10.1093/intimm/2.3.209. [DOI] [PubMed] [Google Scholar]
  13. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  14. Kisielow P., Leiserson W., Von Boehmer H. Differentiation of thymocytes in fetal organ culture: analysis of phenotypic changes accompanying the appearance of cytolytic and interleukin 2-producing cells. J Immunol. 1984 Sep;133(3):1117–1123. [PubMed] [Google Scholar]
  15. MacDonald H. R., Budd R. C., Howe R. C. A CD3- subset of CD4-8+ thymocytes: a rapidly cycling intermediate in the generation of CD4+8+ cells. Eur J Immunol. 1988 Apr;18(4):519–523. doi: 10.1002/eji.1830180405. [DOI] [PubMed] [Google Scholar]
  16. MacDonald H. R., Hengartner H., Pedrazzini T. Intrathymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment. Nature. 1988 Sep 8;335(6186):174–176. doi: 10.1038/335174a0. [DOI] [PubMed] [Google Scholar]
  17. Matsumoto K., Yoshikai Y., Matsuzaki G., Asano T., Nomoto K. A novel CD3-J11d+ subset of CD4+CD8- cells repopulating thymus in radiation bone marrow chimeras. Eur J Immunol. 1989 Jul;19(7):1203–1207. doi: 10.1002/eji.1830190708. [DOI] [PubMed] [Google Scholar]
  18. Nikolić-Zugić J., Moore M. W., Bevan M. J. Characterization of the subset of immature thymocytes which can undergo rapid in vitro differentiation. Eur J Immunol. 1989 Apr;19(4):649–653. doi: 10.1002/eji.1830190412. [DOI] [PubMed] [Google Scholar]
  19. Pardoll D. M., Fowlkes B. J., Bluestone J. A., Kruisbeek A., Maloy W. L., Coligan J. E., Schwartz R. H. Differential expression of two distinct T-cell receptors during thymocyte development. Nature. 1987 Mar 5;326(6108):79–81. doi: 10.1038/326079a0. [DOI] [PubMed] [Google Scholar]
  20. Paterson D. J., Williams A. F. An intermediate cell in thymocyte differentiation that expresses CD8 but not CD4 antigen. J Exp Med. 1987 Nov 1;166(5):1603–1608. doi: 10.1084/jem.166.5.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Penit C., Vasseur F. Cell proliferation and differentiation in the fetal and early postnatal mouse thymus. J Immunol. 1989 May 15;142(10):3369–3377. [PubMed] [Google Scholar]
  22. Scollay R., Shortman K. Identification of early stages of T lymphocyte development in the thymus cortex and medulla. J Immunol. 1985 Jun;134(6):3632–3642. [PubMed] [Google Scholar]
  23. Shortman K., Wilson A., Egerton M., Pearse M., Scollay R. Immature CD4- CD8+ murine thymocytes. Cell Immunol. 1988 May;113(2):462–479. doi: 10.1016/0008-8749(88)90042-1. [DOI] [PubMed] [Google Scholar]
  24. Wilson A., Day L. M., Scollay R., Shortman K. Subpopulations of mature murine thymocytes: properties of CD4-CD8+ and CD4+CD8- thymocytes lacking the heat-stable antigen. Cell Immunol. 1988 Dec;117(2):312–326. doi: 10.1016/0008-8749(88)90121-9. [DOI] [PubMed] [Google Scholar]
  25. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES