ANTI-APOPTOTIC EFFECT OF CD95 RECEPTOR IN NA VE CD8+ T-LYMPHOCYTES IN CHILDREN WITH ACUTE INFECTIOUS MONONUCLEOSIS

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Abstract

Acute infectious mononucleosis is a widespread viral disease, which most often manifests in childhood. The development of acute infectious mononucleosis is accompanied by the change of the CD4+/CD8+ T-lymphocytes ratio and the increase of the virus-specific CD8+ cytotoxic T-lymphocytes number. One of the T-lymphocytes number regulation mechanisms is the modulation of their progenitor cells apoptosis. The death receptor CD95 takes part in the regulation of T-lymphocytes apoptosis, including naïve T-cells. We studied the effect of CD95 receptor activation on apoptosis of naïve CD4+ and naïve cytotoxic CD8+ T-lymphocytes in healthy children and children with acute infectious mononucleosis. In this study children with acute infectious mononucleosis at the age of 9 to 16 years were included. For comparison healthy children of the same age with no clinical and laboratory signs of the disease were used. Naïve CD4+ and naïve cytotoxic CD8+ T-lymphocytes were isolated by negative magnetic immunoseparation. The analysis of naïve T-cells apoptosis and the CD95 receptor surface expression density was performed by using the flow cytometry analysis. The analysis of T-cells was performed in three variants: freshly isolated naïve CD4+ T-lymphocytes and naïve cytotoxic CD8+ T-lymphocytes, and also cells after 24 hours of the cultivation with anti-CD95 monoclonal antibodies or without them. In healthy children both CD95– and CD95+ naïve CD4+ T-lymphocytes underwent apoptosis. In children with acute infectious mononucleosis CD95– naïve CD4+ T-lymphocytes lost their susceptibility to apoptosis induction. In healthy children and children with acute infectious mononucleosis CD95– naïve cytotoxic CD8+ T-lymphocytes were resistant to apoptosis in contrast to CD95+ naïve CD4+ T-lymphocytes. In healthy children CD95 receptor did not induce apoptosis of isolated naïve CD4+ T-lymphocytes and naïve cytotoxic CD8+ T-lymphocytes. In children with acute infectious mononucleosis CD95 receptor was involved in inhibition of apoptosis of naïve cytotoxic CD8+ T-lymphocytes and did not effect on the level of apoptosis of naïve CD4+ T-lymphocytes. We suggest that CD95-dependent suppression of naïve cytotoxic CD8+ T-lymphocytes apoptosis is a protective mechanism for the maintenance of a sufficient number of cytotoxic T-lymphocytes in the blood for the realization of effective antiviral immune response.

About the authors

E. N. Filatova

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation

Author for correspondence.
Email: filatova@nniiem.ru

PhD (Biology), Leading Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation;

Россия

E. V. Anisenkova

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

Junior Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation;

Россия

N. B. Presnyakova

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation;

Россия

T. D. Sycheva

Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

Resident Physician, Department of Children Infections, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation;

Россия

E. A. Kulova

Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

PhD (Medicine), Assistant Professor, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Россия

O. V. Utkin

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation;
Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

PhD (Biology), Head of the Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology;
Associate Professor, Department of Microbiology and Immunology, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation.

Россия

References

  1. Сомова Л.М., Беседнова Н.Н., Плехова Н.Г. Апоптоз и инфекционные болезни // Инфекция и иммунитет. 2014. Т. 4, № 4. С. 303–318. [Somova L.M., Besednova N.N., Plekhova N.G. Apoptosis and infectious diseases. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2014, vol. 4, no. 4, pp. 303–318. doi: 10.15789/2220-7619-2014-4-303-318 (In Russ.)]
  2. Филатова Е.Н., Уткин О.В., Анисенкова Е.В., Преснякова Н.Б., Сычева Т.Д., Краснов В.В., Сенягина Н.Е., Кулова Е.А., Ефимов Е.И. Оценка уровня апоптоза наивных CD8+ T-лимфоцитов у детей с острым инфекционным мононуклеозом при активации рецепторов CD95 и DR3 // Современные технологии в медицине. 2015. Т. 7, № 3. С. 109–118. [Filatova Е.N., Utkin О.V., Anisenkova Е.V., Presnyakova N.B., Sycheva Т.D., Krasnov V.V., Senyagina N.Е., Kulova Е.А., Efimov Е.I. Assessment of apoptosis level of naive CD8+ T-lymphocytes in children with acute infectious mononucleosis in CD95 and DR3 receptors activation. Sovremennye tehnologii v medicine = Modern Technologies in Medicine, 2015, vol. 7, no. 3, pp. 109–118. doi: 10.17691/stm2015.7.3.16 (In Russ.)]
  3. Электронный эпидемиологический атлас Приволжского федерального округа [Electronic epidemiological atlas of the Volga Federal District]. URL: http://epid-atlas.nniiem.ru (дата обращения: 20.01.2016)
  4. Alderson M.R., Armitage R.J., Maraskovsky E., Tough T.W., Roux E., Schooley K., Ramsdell F., Lynch D.H. Fas transduces activation signals in normal human T lymphocytes. J. Exp. Med., 1993, vol. 178, no. 6, pp. 2231–2235.
  5. Balfour H.H., Dunmire S.K., Hogquist K.A. Infectious mononucleosis. Clin. Transl. Immunol., 2015, vol. 4, no. 2, e:33. doi: 10.1038/cti.2015.1
  6. Budd R.C. Death receptors couple to both cell proliferation and apoptosis. J. Clin. Invest., 2002, vol. 109, no. 4, pp. 437–442.
  7. Desbarats J., Wade T., Wade W.F., Newell M.K. Dichotomy between na ve and memory CD4(+) T cell responses to Fas engagement. Proc. Natl. Acad. Sci. USA, 1999, vol. 96, no. 14, pp. 8104–8109.
  8. Gastwirth J.L., Gel Y.R., Hui W.L.W., Lyubchich V., Miao W., Noguchi K. lawstat: an R package for biostatistics, public policy, and law. Version 2.4.1, 2013. URL: https://cran.r-project.org/web/packages/lawstat/index.html
  9. Hapuarachchi T., Lewis J., Callard R.E. A mechanistic model for naive CD4 T cell homeostasis in healthy adults and children. Front. Immunol., 2013, vol. 4, no. 366. doi: 10.3389/fimmu.2013.00366
  10. Hislop A.D., Taylor G.S., Sauce D., Rickinson A.B. Cellular responses to viral infection in humans: lessons from Epstein–Barr virus. Annu. Rev. Immunol., 2007, vol. 25, pp. 587–617. doi: 10.1146/annurev.immunol.25.022106.141553
  11. Hothorn T., Bretz F., Westfall P. Simultaneous inference in general parametric models. Biom. J., 2008, vol. 50, no. 3, pp. 346–363. doi: 10.1002/bimj.200810425
  12. Janols H., Bredberg A., Thuvesson I., Janciauskiene S., Grip O., Wullt M. Lymphocyte and monocyte flow cytometry immunophenotyping as a diagnostic tool in uncharacteristic inflammatory disorders. BMC Infect. Dis., 2010, vol. 10, no. 1, pp. 1–9. doi: 10.1186/1471-2334-10-205
  13. Karcheva M., Lukanov T., Gecheva S., Slavcheva V., Veleva G., Nachev R. Infectious mononucleosis diagnostic potentials. J. IMAB, 2008, vol. 14, no. 1, pp. 9–13.
  14. Kimura M.Y., Pobezinsky L.A., Guinter T., Thomas J., Adams A., Park J.H., Tai X., Singer A. IL-7 signaling must be intermittent, not continuous, during CD8 T cell homeostasis to promote cell survival instead of cell death. Nat. Immunol., 2013, vol. 14, no. 2, pp. 143–151. doi: 10.1038/ni.2494
  15. Le Meur N., Hahne F., Ellis B., Haaland P. flowCore: Basic structures for flow cytometry data. R package version 3.1.1., 2014. URL: http://bioconductor.org/packages/release/bioc/html/flowCore.html
  16. Long H.M., Chagoury O.L., Leese A.M., Ryan G.B., James E., Morton L.T., Abbott R.J.M., Sabbah S., Kwok W., Rickinson A.B. MHC II tetramers visualize human CD4+ T cell responses to Epstein–Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response. J. Exp. Med., 2013, vol. 210, no. 5, pp. 933–949. doi: 10.1084/jem.20121437
  17. Mao J.Q., Yang S.L., Song H., Zhao F.Y., Xu X.J., Gu M.E., Tang Y.M. Clinical and laboratory characteristics of chronic active Epstein–Barr virus infection in children. Zhongguo Dang Dai Er Ke Za Zhi, 2014, vol. 16, no. 11, pp. 1081–1085.
  18. Moss D.J., Bishop C.J., Burrows S.R., Ryan J.M. T lymphocytes in infectious mononucleosis. I. T cell death in vitro. Clin. Exp. Immunol., 1985, vol. 60, no. 1, pp. 61–69.
  19. Palendira U., Low C., Chan A., Hislop A.D., Ho E., Phan T.G., Deenick E., Cook M.C., Riminton D.S., Choo S., Loh R., Alvaro F., Booth C., Gaspar H.B., Moretta A., Khanna R., Rickinson A.B., Tangye S.G. Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP. PLoS Biol., 2011, vol. 9, no. 11, e:1001187. doi: 10.1371/journal.pbio.1001187
  20. Paulsen M., Janssen O. Pro- and anti-apoptotic CD95 signaling in T cells. Cell Commun. Signal, 2011, vol. 9, no. 7. doi: 10.1186/1478-811X-9-7
  21. Pinheiro J., Bates D., DebRoy S., Sarkar D., R Core Team. nlme: Linear and Nonlinear Mixed Effects Models. Version 3.1-117, 2014. URL: https://cran.r-project.org/web/packages/nlme/index.html
  22. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2014. URL: https://www.r-project.org
  23. R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2009. URL: https://www.r-project.org
  24. RStudio Team. RStudio: integrated development for R. RStudio, Inc., Boston, MA, 2015. URL: https://www.rstudio.com/products/rstudio
  25. Sato T., Hirasawa A., Kawabuchi Y., Nishikawa T., Wakabayashi Y. Cellular expressions and serum concentrations of Fas ligand and Fas receptor in patients with infectious mononucleosis. Int. J. Hematol., 2000, vol. 72, no. 3, pp. 329–336.
  26. Scherrenburg J., Piriou E.R.W.A.N., Nanlohy N.M., Van Baarle D. Detailed analysis of Epstein–Barr virus-specific CD4+ and CD8+ T cell responses during infectious mononucleosis. Clin. Exp. Immunol., 2008, vol. 153, no. 2, pp. 231–239. doi: 10.1111/j.1365-2249.2008.03699.x
  27. Shapiro M., Duca K., Lee K., Delgado-Eckert E., Hawkins J., Jarrah A.S., Laubenbacher R., Polys N.F., Hadinoto V., Thorley-Lawson D.A. A virtual look at Epstein–Barr virus infection: simulation mechanism. J. Theor. Biol., 2008, vol. 252, no. 4, pp. 633–648. doi: 10.1016/j.jtbi.2008.01.032
  28. Sulik A., Oldak E., Kroten A., Lipska A., Radziwon P. Epstein–Barr virus effect on frequency of functionally distinct T cell subsets in children with infectious mononucleosis. Adv. Med. Sci., 2014, vol. 59, no. 2, pp. 227–231. doi: 10.1016/j.advms.2014.04.003
  29. Tanaka M., Suda T., Takahashi T., Nagata S. Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J., 1995, vol. 14, pp. 1129–1135.
  30. Tanner J.E., Alfieri C. Epstein–Barr virus induces Fas (CD95) in T cells and Fas ligand in B cells leading to T-cell apoptosis. Blood, 1999, vol. 94, no. 6, pp. 3439–3447.
  31. Van den Heuvel D., Jansen M.A.E., Dik W.A., Bouallouch-Charif H., Zhao D., Van Kester K.A.M., Smits-Te Nijenhuis M.A.W., Kolijn-Couwenberg M.J., Jaddoe V.W.V., Arens R., Van Dongen J.J.M., Moll H.A., Van Zelm M.C. Cytomegalovirus- and Epstein–Barr virus-induced T-cell expansions in young children do not impair naive T-cell populations or vaccination responses: the generation R study. J. Infect. Dis., 2015, vol. 213, no. 2, pp. 233–242. doi: 10.1093/infdis/jiv369
  32. Wickham H. ggplot2: elegant graphics for data analysis. New York: Springer, 2009, 182 p.
  33. Womack J., Jimenez M. Common questions about infectious mononucleosis. Am. Fam. Physic., 2015, vol. 91, no. 6, pp. 372–376.
  34. Xing Y., Song H.M., Wei M., Liu Y., Zhang Y.H., Gao L. Clinical significance of variations in levels of Epstein–Barr virus (EBV) antigen and adaptive immune response during chronic active EBV infection in children. J. Immunotoxicol., 2013, vol. 10, no. 4, pp. 387–392. doi: 10.3109/1547691X.2012.758199

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Copyright (c) 2016 Filatova E.N., Anisenkova E.V., Presnyakova N.B., Sycheva T.D., Kulova E.A., Utkin O.V.

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