SUBPOPULATION LYMPHOCYTE STRUCTURE IN EXPERIMENTAL MOUSE INFECTION CAUSED BY VARIANTS OF ONE TICK-BORNE ENCEPHALITIS VIRUS STRAIN

Abstract

Aim. To study the immunophenotypical peculiarities of mice lymphocytes in experimental infection caused by clones 57 and 58, as the variants of one Tick-borne encephalitis virus (TBEV) strain. Materials and methods. The influence of variants 57 and 58, extracted from the population of one TBEV strain, on immunophenotypical peculiarities of infected mice lymphocytes was studied. Results. In our study, variants 57 and 58 were close by their effect on the structure of lymphocyte subpopulations. The viruses did not influence T lymphocyte number, but in this or that extent, they caused decrease in the number of NKT ( p < 0,05) and T-regulatory cells ( p < 0,05). Both variants also elevated ( p < 0,05) the level of cells with early activation marker (CD45/CD25). The specific feature of variant 57 was induction of B lymphocyte number (CD45/CD/19, p < 0,05). Mixed infection of animals with variants 57 and 58 induced disbalance of immune response, characterized by fall in the number of T lymphocyte, T helper, NK cell pools and rise in B lymphocyte level. Conclusions. Thus, the ability of TBEV variants, as the components of one viral population, to modulate effector functions of hereditary and adaptive immunity at early stages of infectious process was demonstrated.

Keywords

Tick-borne encephalitis / immune response / lymphocytes / experimental infection

References

[1] Ахматова Н. К., Киселевский М. В. Врожденный иммунитет: противоопухолевый и противоинфекционный. М.: Практическая медицина 2008; 256.

[2] Исаков В. А. Клинико-патогенетические аспекты тяжелого гриппа. Аллергология и иммунология 2004; 3 (1): 136-144.

[3] Крылова Н. В. Клеточные и молекулярные механизмы противовирусной защиты при клещевом энцефалите: дис. … д-ра мед. наук. М. 2014; 229.

[4] Юсупова Р. Ш., Сибиряк С. В., Каюмова Э. Ю., Сибиряк Д. С. Экспрессия Fas-антигена на лимфоцитах периферической крови и антигенспецифический апоптоз лимфоцитов при туберкулезе легких. Мед. иммунология 2000; 2 (2): 205-206.

[5] Bhardwaj N. Harnessing the immune system to treat cancer. J. Clin. Invest 2007; 117 (5): 1130-1136.

[6] Chiba N. Pathogenicity of tick-borne encephalitis virus isolated in Hokkaido, Japan in mouse model. Vaccine 1999; 17: 779-787.

[7] Diefenbach A., Raulet D. H. The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol. Rev. 2002; 188: 9-21.

[8] Dörrbecker B., Dobler G., Spiegel M., Hufert F. T. Tick-borne encephalitis virus and the immune response of the mammalian host. Travel. Med. Infect. Dis. 2010; 8 (4): 213-222.

[9] Duwaerts C. C., Sun E. P., Cheng C. W., van Rooijen N., Gregory S. H. Cross-activating invariant NKT cells and kupffer cells suppress cholestatic liver injury in a mouse model of biliary obstruction. PLoS One 2013; 8 (11): e79702.

[10] Hall B. M., Tran G. T., Robinson C. M., Hodgkinson S. J. Induction of antigen specific CD4+CD25+Foxp3+T regulatory cells from naïve natural thymic derived T regulatorycells. Int. Immunopharmacol. 2015; pii: S1567-5769(15)00151-4.

[11] Hayasaka D. Mortality following peripheral infection with tick-borne encephalitis virus results from a combination of central nervous system pathology, systemic inflammatory and stress responses. Virology 2009; 390: 139-150.

[12] Hudspeth K., Pontarini E., Tentorio P., Cimino M., Donadon M., Torzilli G. The role of natural killer cells in autoimmune liver disease: A comprehensive review. J. Autoimmun 2013; 46: 55-65.

[13] Matsuoka H., Fujimura T., Mori et al. Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells. Int. Immunopharmacol 2007; 7 (11): 1422-32.

[14] Overby A. K., Popov V. L., Niedrig M., Weber F. Tick-borne encephalitis virus delays interferon induction and hides its double-stranded RNA in intracellular membrane vesicles. Journal of virology 2010; 84 (17): 8470-8483.

[15] Palus M., Bílý T., Elsterová J., Langhansová H., Salát J., Vancová M., Růžek D. Infection and injury of human astrocytes by tick-borne encephalitis virus. J. Gen. Virol. 2014; 95 (11): 2411-2426.

[16] Preza G. C., Yang O. O., Elliott J., Anton P. A., Ochoa M. T. T lymphocyte density and distribution in human colorectal mucosa, and inefficiency of current cell isolation protocols. PLoS One 2015; 10 (4): e0122723.

[17] Robertson S. J., Mitzel D. N., Taylor R. T., Best S. M., Bloom M. E. Tick-borne flaviviruses: dissecting host immune responses and virus countermeasures. Immunol. Res. 2009; 43 (1-3): 172-186.

[18] Savage P. B. Vaccine development: NKT-cell adjuvants in conjugate. Nat. Chem. Biol. 2014; 10 (11): 882-883.

[19] Takeda K., Okumura K. CAM and NK Cells. eCAM 2004; 1 (1): 17-27.

[20] Xu J., Wu R., Xiang F., Kong Q., Hong J., Kang X. Diversified phenotype of antigen specific CD8+ T cells responding to the immunodominant epitopes of IE and pp65 antigens of human cytomegalovirus. Cell. Immunol. 2015; 295 (2): 105-111.

[21] Yu C., Achazi K., Niedrig M. Tick-borne encephalitis virus triggers inositol-requiring enzyme 1 (IRE1) and transcription factor 6 (ATF6) pathways of unfolded protein response. Virus Res. 2013; 178 (2): 471-477.

RIGHTS & PERMISSIONS

Motuzova O.V., Akhmatova E.A., Khomenkov V.G., Akhmatova N.K., Lebedinskaya O.V., Karganova G.G.