Skip to main content
SpringerLink
Log in

The Effect of TCR-Activation and β-Estradiol on the Maturation and Differentiation of CD45RA+ T cells in vitro

  • Published:
Cell and Tissue Biology Aims and scope Submit manuscript

Abstract—

Cellular and molecular aspects of maturation and differentiation of TCR-activated naive (CD3+CD45RA+CD62L+) T cells exposed to different concentrations of the female sex hormone β-estradiol in vitro were monitored. CD3+CD45RA+CD62L+ T cells were obtained from a fraction of blood mononuclear cells of healthy donors using immunomagnetic separation. The immunophenotype of T lymphocytes was analyzed by flow cytofluorometry. The polymerase chain reaction defined the level of U2af1l4 and Gfi1 gene expression in CD3+CD45RA+CD62L+ T cells. It was found that altered U2af1l4, Gfi1 gene expression produced by β-estradiol affected the maturation and differentiation of CD45RA+CD62L+ T lymphocytes. The cells underwent phenotypic conversion characterized by increased numbers of CD45RO+-T lymphocytes and reduced in content of T cells with molecules of activation and costimulation (CD127 and CD28) on the membrane surface.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Altemus, M., Dhabhar, F.S., and Yang, R., Immune function in PTSD, Ann. N. Y. Acad. Sci., 2006, vol. 1071, pp. 167–183.

    Article  CAS  PubMed  Google Scholar 

  2. Ayroldi, E., Macchiarulo, A., and Riccardi, C., Targeting glucocorticoid side effects: selective glucocorticoid receptor modulator or glucocorticoid-induced leucine zipper? A perspective, FASEB J., 2014, vol. 28, pp. 5055–5070.

    Article  CAS  PubMed  Google Scholar 

  3. Bel, S. and Hooper, L.V., Immunology: a bacterial nudge to T-cell function, Nature, 2015, vol. 526, pp. 328–330.

    Article  CAS  PubMed  Google Scholar 

  4. Butte, J.M., Lee, J.S., Jesneck, J.Keir, M.E., Haining, W.N., and Sharpe, A.H., CD28 costimulation regulates genome-wide effects on alternative splicing, PLoS One, 2012, vol. 7, no. 6. e40032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cheng, Q., Morand, E., and Yang, Y.H., Development of novel treatment strategies for inflammatory diseases- similarities and divergence between glucocorticoids and GILZ, Front. Pharmacol., 2014, vol. 5, p. 169. doi 10.3389/fphar.2014.00169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Finlay-Schultz, J. and Sartorius, C.A., Steroid hormones, steroid receptors, and breast cancer stem cells, J. Mammary Gland. Biol. Neoplasia, 2015, vol. 20, pp. 39–50.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Furman, D., Sexual dimorphism in immunity: improving our understanding of vaccine immune responses in men, Expert Rev. Vaccines, 2015, vol. 14, pp. 461–471.

    Article  CAS  PubMed  Google Scholar 

  8. Furman, D., Hejblum, B.P., Simon, N., Jojic, V., Dekker, C.L., Thiébaut, R., Tibshirani, R.J., and Davis, M.M., Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination, Proc. Natl. Acad. Sci. U. S. A., 2014, vol. 111, pp. 869–874.

    Article  CAS  PubMed  Google Scholar 

  9. Giefing-Kröll, C., Berger, P., Lepperdinger, G., and Grubeck-Loebenstein, B., How sex and age affect immune responses, susceptibility to infections, and response to vaccination, Aging Cell, 2015, vol. 14, pp. 309–321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gruver-Yates, A.L. and Cidlowski, J.A., Tissue-specific actions of glucocorticoids on apoptosis: a double- edged sword, Cells, 2013, vol. 2, pp. 202–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gutsol, A.A., Sohonevich, N.A., and Litvinova, L.S., Effect of dexamethasone on the activation of memory T cells and naive T lymphocytes, Vestn. Ural. Med. Akad. Nauki, 2012, vol. 4, no. 41, p. 29.

    Google Scholar 

  12. Harris, N., Immunology: chronic effects of acute infections, Nature, 2015, vol. 526, pp. 509–510.

    Article  CAS  PubMed  Google Scholar 

  13. Heyd, F. and Lynch, W.K., Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing, Mol. Cell, 2010, vol. 40, pp. 126–137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Heyd, F., ten Dam, G., and Möröy, T., Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing, Nat. Immunol., 2006, vol. 7, pp. 859–867.

    Article  CAS  PubMed  Google Scholar 

  15. Khaziakhmatova, O.G., The role of steroid hormones in the differentiation of T-lymphocytes: molecular genetic and immuno-morphological aspects, Extended Abstract of Cand. Sci. Dissertation, Tomsk, 2016.

  16. Kudryavtsev, I.V., T-cell memory: the main population and the stages of differentiation, Russ. Immunol. Zh., 2014, vol. 8, no. 4–17, pp. 947–964.

  17. Laffont, S., Rouquié, N., Azar, P., Seillet, C., Plumas, J., Aspord, C., and Guéry, J.C., X-chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women, J. Immunol., 2014, vol. 193, pp. 5444–5452.

    Article  CAS  PubMed  Google Scholar 

  18. Lai, J.J., Lai, K.P., Zeng, W., Chuang, K.H., Altuwaijri, S., and Chang, C., Androgen receptor influences on body defense system via modulation of innate and adaptive immune systems: lessons from conditional AR knockout mice, Am. J. Pathol., 2012, vol. 181, pp. 1504–1512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Litvinova, L.S., Seledtsov, V.I., Shupletsova, V.V., Gutsol, A.A., and Anishchenko, Ye.S., Steroid regulation of immune memory, Vestn. Balt. Fed. Univ. im. I. Kanta, 2011, vol. 1, pp. 77–87.

    Google Scholar 

  20. Litvinova, L.S., Mazunin, I.O., Gutsol, A.A., Sokhonevich, N.A., Khaziakhmatova, O.G., and Kofanova, K.A., Dose-response effect of steroid hormones on Gfi1 and U2af1l4 gene expression in T lymphocytes at different stages of differentiation, Mol. Biol. (Moscow), 2013a, vol. 47, no. 4, pp. 572–580.

    Article  CAS  Google Scholar 

  21. Litvinova, L.S., Sokhonevich, N.A., Gutsol, A.A., and Kofanova, K.A., The influence of immunoregulatory cytokines IL-2, IL-7, and IL-15 upon activation, proliferation, and apoptosis of immune memory T-cells in vitro, Cell Tissue Biol., 2013b, vol. 7, no. 6, pp. 539–544.

    Article  Google Scholar 

  22. Litvinova, L.S., Gutsol, A.A., Sohonevich, N.A., Shupletsova, V.V., Kofanova, K.A., Kaygorodova, E.V., and Goncharov, A.G., The main surface markers of the functional activity of T-lymphocytes, Med. Immunol., 2014, vol. 6, no. 1, pp. 7–26.

    Article  Google Scholar 

  23. McNeill, L., Salmond, R.J., Cooper, J.C., Carret, C.K., Cassady-Cain, R.L., Roche-Molina, M., Tandon, P., Holmes, N., and Alexander, D.R., The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses, Immunity, 2007, vol. 27, pp. 425–437.

    Article  CAS  PubMed  Google Scholar 

  24. Motta-Mena, B.L., Heyd, F., and Lynch, W.K., Context-dependent regulatory mechanism of the splicing factor HnRNP L, Mol. Cell, 2010, vol. 37, pp. 223–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Park, J.H., Yu, Q., Erman, B., Appelbaum, J.S., Montoya-Durango, D., Grimes, H.L., and Singer, A., Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival, Immunity, 2004, vol. 21, pp. 289–302.

    Article  CAS  PubMed  Google Scholar 

  26. Peterson, M.P., Rosvall, K.A., Choi, J.H., Ziegenfus, C., Tang, H., Colbourne, J.K., and Ketterson, E.D., Testosterone affects neural gene expression differently in male and female juncos: a role for hormones in mediating sexual dimorphism and conflict, PLoS One, 2013, vol. 8, no. 4. e61784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pfaffl, M.W., A new mathematical model for relative quantification in real-time RT-PCR, Nucleic Acids Res., 2001, vol. 29. e45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Priyanka, H.P., Krishnan, H.C., Singh, R.V., Hima, L., and Thyagarajan, S., Estrogen modulates in vitro T cell responses in a concentration- and receptor-dependent manner: effects on intracellular molecular targets and antioxidant enzymes, Mol. Immunol., 2013, vol. 56, pp. 328–339.

    Article  CAS  PubMed  Google Scholar 

  29. Surh, C.D. and Sprent, J., Homeostasis of naive and memory T cells, Immunity, 2008, vol. 29, pp. 848–862.

    Article  CAS  PubMed  Google Scholar 

  30. Todosenko, N.M., Koroleva, Yu.A., Khaziahmatova, O.G., Yurova, K.A., and Litvinova, L.S., Genomic and non-genomic effects of glucocorticoids, Geny Kletki, 2017, vol. 12, no. 1, pp. 27–33.

    Google Scholar 

  31. Van Mens, S.P., Meijvis, S.C., Grutters, J.C., Vlaminckx, B.J.M., Bos, W.J.W., and Rijkersa, G.T., Dexamethasone treatment has no effect on the formation of pneumococcal antibodies during community-acquired pneumonia, Clin. Vaccine Immunol., 2012, vol. 19, pp. 811–813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wieckowski, E.U., Visus, C., Szajnik, M., Szczepanski, M.J., Storkus, W.J., and Whiteside, T.L., Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes, J. Immunol., 2009, vol. 183, pp. 3720–3730.

    Article  CAS  PubMed  Google Scholar 

  33. Wu, Z., Yates, A.L., Hoyne, G.F., and Goodnow, C.C., Consequences of increased CD45RA and RC isoforms for TCR signaling and peripheral T cell deficiency resulting from heterogeneous nuclear ribonucleoprotein L-like mutation, J. Immunol., 2010, vol. 185, pp. 231–238.

    Article  CAS  PubMed  Google Scholar 

  34. Yurova, K.A., The role of cytokines with common receptor γ chain (IL-2, IL-7, IL-15) in regulating the mechanisms of molecular genetic control of T cell differentiation, Extended Abstract of Cand. Sci. Dissertation, Tomsk, 2015.

  35. Zhao, S., Zhu, W., Xue, S., and Han, D., Testicular defense systems: immune privilege and innate immunity, Cell Mol. Immunol., 2014, vol. 11, pp. 428–437.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zilbernagl, S. and Despopoulos, A., Naglyadnaya fiziologiya (IIlusrative Physiology), Moscow: Binom. Laboratoriya Znanii, 2013.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Basic Laboratory of Immunology and Cell Biotechnologies, Immanuel Kant Baltic Federal University, 236029, Kaliningrad, Russia

    O. G. Khaziakhmatova, K. A. Yurova, N. M. Todosenko & L. S. Litvinova

Authors
  1. O. G. Khaziakhmatova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. A. Yurova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. M. Todosenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. S. Litvinova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. S. Litvinova.

Additional information

Translated by I. Fridlyanskaya

Abbreviations: MNC—mononuclear cell, Ac—TCR-activator, Est—β–estradiol.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khaziakhmatova, O.G., Yurova, K.A., Todosenko, N.M. et al. The Effect of TCR-Activation and β-Estradiol on the Maturation and Differentiation of CD45RA+ T cells in vitro. Cell Tiss. Biol. 12, 448–454 (2018). https://doi.org/10.1134/S1990519X18060032

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990519X18060032

Keywords:

Search

Navigation