• Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:

Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells

Thymalin is a polypeptide complex isolated from the thymus and regulating the functions of the immune system. Thymalin is effective in therapy of acute respiratory syndrome, chronic obstructive bronchitis, and other immunopathology. Thymalin increases functional activity of T lymphocytes, but the targeted molecular mechanism of its biological activity requires further study. We studied the influence of thymalin on differentiation of human hematopoietic stem cells (HSC) and expression of CD28 molecule involved in the implementation of antiviral immunity in COVID-19 infection. It was found that thymalin reduced the expression of CD44 (stem cell marker) and CD117 (molecule of the intermediate stage of HSC differentiation) by 2-3 times and increased the expression of CD28 (marker of mature T lymphocytes) by 6.8 times. This indirectly indicates that thymalin stimulated differentiation of CD117+ cells into mature CD28+T lymphocytes. It is known that in patients with severe COVID-19, the number of CD28+, CD4+, CD8+T lymphocytes in the blood decreased, which attested to a pronounced suppression of immunity. It is possible that the antiviral effect of thymalin consists in compensatory stimulation of HSC differentiation into CD28+T lymphocytes at the stage of immunity suppression in unfavorable course of viral infection. Thymalin can be considered as an immunoprotective peptide drug for the prevention of COVID-19.

References

  1. 1.

    Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139-149.

    CAS  Article  Google Scholar 

  2. 2.

    Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J. Hematol. Oncol. 2018;11(1):64. doi: https://doi.org/10.1186/s13045-018-0605-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Frumento G, Zuo J, Verma K, Croft W, Ramagiri P, Chen FE, Moss P. CD117 (c-Kit) is expressed during CD8+ T cell priming and stratifies sensitivity to apoptosis according to strength of TCR engagement. Front. Immunol. 2019;10:468. doi: https://doi.org/10.3389/fimmu.2019.00468

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Godoy GJ, Paira DA, Olivera C, Breser ML, Sanchez LR, Motrich RD, Rivero VE. Differences in T regulatory cells between mouse strains frequently used in immunological research: Treg cell quantities and subpopulations in NOD, B6 and BALB/c mice. Immunol. Lett. 2020;223:17-25.

    CAS  Article  Google Scholar 

  5. 5.

    Khavinson V, Linkova N, Diatlova A, Trofimova S. Peptide regulation of cell differentiation. Stem Cell Rev. Rep. 2020;16(1):118-125.

    CAS  Article  Google Scholar 

  6. 6.

    Khavinson VKh. Peptides and ageing. Neuroendocrinol. Lett. 2002;23(Suppl. 3):11-144.

    PubMed  Google Scholar 

  7. 7.

    Khlystova ZS, Kalinina II, Shmeleva SP. Thymalin in developing respiratory organs of human fetus. Bull. Exp. Biol. Med. 2003;135(6):600-602.

    CAS  Article  Google Scholar 

  8. 8.

    Kim KH, Kim HK, Kim HD, Kim CG, Lee H, Han JW, Choi SJ, Jeong S, Jeon M, Kim H, Koh J, Ku BM, Park SH, Ahn MJ, Shin EC. PD-1 blockade-unresponsive human tumorinfiltrating CD8+ T cells are marked by loss of CD28 expression and rescued by IL-15. Cell Mol. Immunol. 2020. doi: https://doi.org/10.1038/s41423-020-0427-6

  9. 9.

    Li JP, Hsieh MJ, Chou YE, Chao YH, Tsao TC, Yang SF. CD44 gene polymorphisms as a risk factor for susceptibility and their effect on the clinicopathological characteristics of lung adenocarcinoma in male patients. Int. J. Environ. Res. Public Health. 2020;17(9):2981. doi:https://doi.org/10.3390/ijerph17092981

    CAS  Article  PubMed Central  Google Scholar 

  10. 10.

    Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033-1034.

    CAS  Article  Google Scholar 

  11. 11.

    Morath I, Hartmann TN, Orian-Rousseau V. CD44: more than a mere stem cell marker. Int. J. Biochem. Cell Biol. 2016;81(Pt A):166-173.

    CAS  Article  Google Scholar 

  12. 12.

    Myburgh R, Kiefer JD, Russkamp NF, Magnani CF, Nuñez N, Simonis A, Pfister S, Wilk CM, McHugh D, Friemel J, Müller AM, Becher B, Münz C, van den Broek M, Neri D, Manz MG. Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells. Leukemia. 2020. doi: https://doi.org/10.1038/s41375-020-0818-9

  13. 13.

    Scavone C, Brusco S, Bertini M, Sportiello L, Rafaniello C, Zoccoli A, Berrino L, Racagni G, Rossi F, Capuano A. Current pharmacological treatments for COVID-19: what’s next? Br. J. Pharmacol. 2020. doi:https://doi.org/10.1111/bph.15072

  14. 14.

    Wang F, Hou H, Luo Y, Tang G, Wu S, Huang M, Liu W, Zhu Y, Lin Q, Mao L, Fang M, Zhang H, Sun Z. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight. 2020;5(10):e137799. doi: https://doi.org/10.1172/jci.insight.137799

    Article  PubMed Central  Google Scholar 

  15. 15.

    Zhukova GV, Schikhlyarova AI, Barteneva TA, Shevchenko AN, Zakharyuta FM. Effect of Thymalin on the tumor and thymus under conditions of activation therapy in vivo. Bull. Exp. Biol. Med. 2018;165(1):80-83.

    CAS  Article  Google Scholar 

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Correspondence to N. S. Linkova.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 158-163, September, 2020

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Khavinson, V.K., Linkova, N.S., Kvetnoy, I.M. et al. Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Bull Exp Biol Med 170, 118–122 (2020). https://doi.org/10.1007/s10517-020-05016-z

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Key Words

  • thymalin
  • peptides
  • hematopoietic stem cells
  • cell differentiation
  • COVID-19