European Cytokine Network

, Volume 27, Issue 4, pp 102–107 | Cite as

Direct effects of interleukin-7 on the function of human T cells in vitro

  • Vyacheslav A. Shmarov
  • Vladimir V. Malashchenko
  • Maksim E. Meniailo
  • Natalia D. Gazatova
  • Natalia M. Todosenko
  • Olga B. Melashchenko
  • Andrei G. Goncharov
  • Victor I. Seledtsov
Research Article


CD3+ T lymphocytes were isolated by positive magnetic separation from the peripheral blood of healthy donors. In the absence of any additional activating stimuli, interleukin-7 (IL-7) was shown to augment the levels of T cells expressing CD25 activation marker both in CD4-positive and in CD4-negative effector memory (CD45RA-CD197-) T cell subsets, as well as in terminally differentiated (CD45RA+CD197-) T cells, without significantly affecting the activation status of naive (CD45RA+CD197+) and central memory (CD45RA-CD197+) T cells. In addition, IL-7 noticeably enhanced the production of IL-2, interferon-γ (IFN-γ), and IL-10, but not IL-4, in T cells. The direct effects of IL-7 on T cell activation induced in vitro by MACSiBead™ particles coated with CD2, CD3, and CD28 antibodies (Abs) were also investigated. Upon cell activation, IL-7 significantly augmented the levels of CD25+ T cells in naive (CD45RA+CD197+), central memory (CD45RA-CD197+), and effector memory (CD45RA-CD197-) T-cell compartments. In addition, IL-7 facilitated activation of CD4- (but not CD4+) terminally differentiated effector (CD45RA+CD197-) T cells. Finally, IL-7 was found to upregulate the production of IL-2, IFN-γ, IL-4, and IL-10 by activated T cells. In conclusion, we speculate that IL-7 is capable of enhancing functional T cell activity without causing significant functional inbalance between various T cell subsets.

Key words

interleukin-7 T cell homeostatic activity T-cell activation CD25 cytokine production 









peripheral blood mononuclear cell


helper T cell


regulatory T cell


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  1. 1.
    Elgert K. Immunology: understanding the immune system. New Jersey: Wiley-Blackwell, 2009, 726s.Google Scholar
  2. 2.
    Peschon JJ, Morrissey PJ, Grabstein KH, et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 1994; 180: 1955.CrossRefPubMedGoogle Scholar
  3. 3.
    von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a non-redundant cytokine. J Exp Med 1995; 181: 1519.CrossRefGoogle Scholar
  4. 4.
    Capitini CM, Chisti AA, Mackall CL, Modulating CL. T cell homeostasis with IL-7: preclinical and clinical. J Intern Med 2009; 266: 141.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Surh CD, Sprent J. Homeostasis of naive and memory T cells. Immunity 2008; 29: 848.CrossRefPubMedGoogle Scholar
  6. 6.
    Dadi H, Ke S, Roifman CM. Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor is dependent on protein tyrosine kinase activity. Blood 1994; 84: 1579.PubMedGoogle Scholar
  7. 7.
    Foxwell BM, Beadling C, Guschin D, Kerr I, Cantrell D. Interleukin-7 can induce the activation of Jak 1, Jak 3 and STAT 5 proteins in murine T cells. Eur J Immunol 1995; 25: 3041.CrossRefPubMedGoogle Scholar
  8. 8.
    Lali FV, Crawley J, McCulloch DA, Foxwell BM. A late, prolonged activation of the phosphatidylinositol 3-kinase pathway is required for T cell proliferation. J Immunol 2004; 172: 3527.CrossRefPubMedGoogle Scholar
  9. 9.
    Le Campion A, Pommier A, Delpoux A, et al. IL-2 and IL-7 determine the homeostatic balance between the regulatory and conventional CD4+ T cell compartments during peripheral T cell reconstitution. J Immunol 2012; 189: 3339.CrossRefPubMedGoogle Scholar
  10. 10.
    Simonetta F, Gestermann N, Bloquet S, Bourgeois C. Interleukin-7 optimizes FOXP3+CD4+ regulatory T cells reactivity to interleukin-2 by modulating CD25 expression. PLoS One 2014; 9: e113314.CrossRefGoogle Scholar
  11. 11.
    Geginat J, Lanzavecchia A, Sallusto F. Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines. Blood 2003; 101: 4260.CrossRefPubMedGoogle Scholar
  12. 12.
    Todosenko NM, Shmarov VA, Malashchenko VV, et al. Erythropoietin exerts direct immunomodulatory effects on the cytokine production by activated human T-lymphocytes. Int Immunopharmacol 2016; 36: 277.CrossRefPubMedGoogle Scholar
  13. 13.
    Sin JI, Kim J, Pachuk C, Weiner DB, Patchuk C. Interleukin 7 can enhance antigen-specific cytotoxic-T-lymphocyte and/or Th2-type immune responses in vivo. Clin Diagn Lab Immunol 2000; 7: 751.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Webb LM, Foxwell BM, Feldmann M. Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. Eur J Immunol 1997; 27: 633.CrossRefPubMedGoogle Scholar
  15. 15.
    Yamaki S, Ine S, Kawabe T, et al. OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells. Eur J Immunol 2014; 44: 3015.CrossRefPubMedGoogle Scholar
  16. 16.
    Vakkila J, Aystö S, Saarinen-Pihkala UM, Sariola H. Naive CD4+ T cells can be sensitized with IL-7. Scand J Immunol 2011; 54: 501.CrossRefGoogle Scholar

Copyright information

© John Libbey Eurotext 2016

Authors and Affiliations

  • Vyacheslav A. Shmarov
    • 1
  • Vladimir V. Malashchenko
    • 1
  • Maksim E. Meniailo
    • 1
  • Natalia D. Gazatova
    • 1
  • Natalia M. Todosenko
    • 1
  • Olga B. Melashchenko
    • 1
  • Andrei G. Goncharov
    • 1
  • Victor I. Seledtsov
    • 1
    • 2
  1. 1.Immanuel Kant Baltic Federal UniversityKaliningradRussia
  2. 2.Immanuel Kant Baltic Federal UniversityKaliningradRussia

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