Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

New insights into IL-7 signaling pathways during early and late T cell development

Cellular & Molecular Immunology volume 10, pages 187–189 (2013)Cite this article

IL-7, a cytokine secreted mainly by stromal cells in the bone marrow and thymus, has been recognized to be critical for the development of all lymphocytes.1 However, the underlying mechanisms through which IL-7-mediated signaling contributes to early T-cell development and to mature T-cell maintenance are not yet completely understood. Two recently published studies in Nature Immunology reported that a newly identified IL-7 signaling pathway acts during early T-cell development and documented how IL-7 signaling interacts with the T-cell antigen receptor (TCR) to influence mature T-cell survival.2,3

IL-7 signaling through the IL-7 receptor (IL-7R) plays a critical role in the survival of CD4 and CD8 double-negative (DN) thymocytes during early T-cell development.1,4 DN thymocytes can be divided into four populations known as DN1 (CD44+CD25−), DN2 (CD44+CD25+), DN3 (CD44−CD25+) and DN4 (CD44−CD25−).1,5 The development of T lymphocytes can also be divided into pre-TCR and TCR-dependent stages based on their TCR differentiation status.6 During the pre-TCR stage, T lymphocytes are CD4− and CD8− DN, which consists of the four previously described populations. After the TCR subunits are rearranged and constructed in DN3 and DN4, T lymphocytes progress to the TCR-dependent stage.5,7 T cells with the αβ TCR are generally single positive CD4+ or CD8+ cells, which later become members of the helper or cytotoxic/effector subsets.5,7 Those cells expressing the alternate γδ TCR are negative for T lineage markers and recognize non-peptidic antigens.5,7,8

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Hong C, Luckey MA, Park JH . Intrathymic IL-7: the where, when, and why of IL-7 signaling during T cell development. Semin Immunol 2012; 24: 151–158.

    Article  CAS  Google Scholar 

  2. Patra AK, Avots A, Zahedi RP, Schuler T, Sickmann A, Bommhardt U et al. An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development. Nat Immunol 2013; 14: 127–135.

    Article  CAS  Google Scholar 

  3. Kimura MY, Pobezinsky LA, Guinter TI, Thomas J, Adams A, Park JH et al. IL-7 signaling must be intermittent, not continuous, during CD8+ T cell homeostasis to promote cell survival instead of cell death. Nat Immunol 2013; 14: 143–151.

    Article  CAS  Google Scholar 

  4. Vicente R, Swainson L, Marty-Gres S, de Barros SC, Kinet S, Zimmermann VS et al. Molecular and cellular basis of T cell lineage commitment. Semin Immunol 2010; 22: 270–275.

    Article  CAS  Google Scholar 

  5. Godfrey DI, Kennedy J, Suda T, Zlotnik A . A developmental pathway involving four phenotypically and functionally distinct subsets of CD3−CD4−CD8− triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol 1993; 150: 4244–4252.

    CAS  PubMed  Google Scholar 

  6. Macian F . NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol 2005; 5: 472–484.

    Article  CAS  Google Scholar 

  7. Adachi S, Amasaki Y, Miyatake S, Arai N, Iwata M . Successive expression and activation of NFAT family members during thymocyte differentiation. J Biol Chem 2000; 275: 14708–14716.

    Article  CAS  Google Scholar 

  8. Kim K, Lee CK, Sayers TJ, Muegge K, Durum SK . The trophic action of IL-7 on pro-T cells: inhibition of apoptosis of pro-T1, -T2, and -T3 cells correlates with Bcl-2 and Bax levels and is independent of Fas and p53 pathways. J Immunol 1998; 160: 5735–5741.

    CAS  PubMed  Google Scholar 

  9. Hsu HC, Mountz JD . Metabolic syndrome, hormones, and maintenance of T cells during aging. Curr Opin Immunol 2010; 22: 541–548.

    Article  CAS  Google Scholar 

  10. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R . Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 2003; 4: 1191–1198.

    Article  CAS  Google Scholar 

  11. Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD, Bradley LM . Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med 2003; 198: 1797–1806.

    Article  CAS  Google Scholar 

  12. Kang J, Coles M . IL-7: the global builder of the innate lymphoid network and beyond, one niche at a time. Semin Immunol 2012; 24: 190–197.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Weifang Medical University, Weifang, China

    Na Niu

  2. Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA

    Xuebin Qin

Authors
  1. Na Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuebin Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuebin Qin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niu, N., Qin, X. New insights into IL-7 signaling pathways during early and late T cell development. Cell Mol Immunol 10, 187–189 (2013). https://doi.org/10.1038/cmi.2013.11

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2013.11

This article is cited by

Search

Advanced search

Quick links