SECRETION OF IL-12, IL-27 BY MONONUCLEAR LEUKOCYTES AND EXPRESSION OF THEIR RECEPTORS ON T-LYMPHOCYTES IN CONDITIONS OF DIRECTED CELL INDUCTION IN VITRO IN PULMONARY TUBERCULOSIS
https://doi.org/10.15789/1563-0625-2014-3-237-246
Abstract
The article presents the results of studies concerning secretion of cytokines belonging to interleukin 12 family, i.e., IL-12р70, IL-12р40, IL-12р35 and IL-27 in mononuclear blood leukocytes, as well as expression of their specific receptors on T-lymphocytes from tuberculosis patients under the in vitro conditions of directed (resp., antigen- and cytokine-mediated) cell induction. In patients with pulmonary TB, we have registered suppression of both spontaneous and BCG-induced secretion of IL-12р70 and IL- 12р35, along with overproduction of IL-12р40 and IL-27. Furthermore, a decrease in relative contents of СD3+gp130+,CD3+IL12Rβ2+ lymphocytes were revealed in the in vitro IL-12/IL-27 induction tests, as well as increased concentration of T-cells with high expression of the inhibitory molecule WSX-1 (CD3+WSX-1+hi). It was shown that the detectable changes are unidirectional in most cases, being dependent on clinical form of the disease and sensitivity of the etiological agent to anti-tuberculosis drugs.
About the Authors
I. E. Esimova
Siberian State Medical University, Tomsk
Russian Federation
Russian Federation
PhD (Medicine), Doctoral Candidate, Department of Pathophysiology, Siberian State Medical University
O. I. Urazova
Siberian State Medical University, Tomsk
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor,Department of pathophysiology, Siberian State Medical University
V. V. Novitskiy
Siberian State Medical University, Tomsk
Russian Federation
PhD, MD (Medicine), Full Member, Russian Academy of Sciences
Russian Federation
PhD, MD (Medicine), Full Member, Russian Academy of Sciences
R. R. Khasanova
Siberian State Medical University, Tomsk
Russian Federation
Russian Federation
PhD (Medicine), Doctoral Candidate, Department of Pathophysiology, Siberian State Medical University
O. V. Filinyuk
Siberian State Medical University, Tomsk
Russian Federation
Russian Federation
PhD, MD (Medicine), Associate Professor, Chief, Department of Phthisiology and Pulmonology, Siberian State Medical University
References
1. Gol`dberg E.D., Dygay A.M., Shakhov V.P. Metody kul`tury tkani v gematologii [Tissue culture methods in hematology]. Tomsk, Tomsk University Publishing House, 1992. 264 p.
2. Ivashkin V.T. Osnovnye ponyatiya i polozheniya fundamental`noy immunologii [The basic concepts and provisions of basic immunology]. RZHGGK – Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2008, no. 4, pp. 4-13.
3. Ketlinskiy S.A. Rol` geterodimernykh tsitokinov semeystva IL-12 v razvitii i regulyatsii vrozhdennogo immuniteta i TH1 immunnogo otveta [The role of heterodimeric cytokines of the IL-12 family in the development and regulation of the inborn immunity and TH1 immune response]. Meditsinskiy akademicheskiy zhurnal – Medical Academic Journal, 2005, vol. 5, no. 3, pp. 13-25.
4. Ketlinskiy S.A., Simbirtsev A.S. Tsitokiny [Cytokines]. St. Petersburg, Publishing house the Foliant, 2008. 552 p.
5. Koretskaya N.M. Ostroprogressiruyushchiy tuberkulez legkikh: klinika, diagnostika, lechenie [Acutely progressive pulmonary tuberculosis: clinical features, diagnosis, treatment]. Mezhdunarodnyy zhurnal prikladnykh i fundamental`nykh issledovaniy – International Journal of Applied and Basic Research, 2011, no. 7, pp. 33-34.
6. Koshkina A.A. Mekhanizmy dizregulyatsii retseptoroposredovannoy signal`noy transduktsii v T-limfotsitakh krovi pri tuberkulioze liogkikh [Mechanisms of dysregulation of receptor-signal transduction in T-lymphocytes in pulmonary tuberculosis]. Fundamental`nye issledovaniya – Basic Research, 2012, part 1, no. 8, pp. 91-95.
7. Simbirtsev A.S. Rol` tsitokinov v regulyatsii fiziologicheskikh funktsiy immunnoy sistemy [The role of cytokines in the regulation of physiological functions of the immune system]. Fiziologiya i patologiya immunnoy sistemy – Physiology and Pathology of the Immune System, 2004, no. 10, pp. 3-10.
8. Churina E.G., Novitskiy V.V., Urazova O.I. Faktory immunosupressii pri razlichnykh patologiyakh [Factors of immunosuppression in various pathologies]. Byulleten` sibirskoy meditsiny – Bulletin of the Siberian Medicine, 2012, no. 4, pp. 103-111.
9. Churina E.G., Urazova O.I., Novitskiy V.V. Regulyatornye T-kletki. Immunosupressornye effekty pri tuberkuleze legkikh [Regulatory T cells. Immunosuppressive effects of pulmonary tuberculosis]. Saarbrucken: LAPLAMBERT Academic Pablishing Gmb H&Co, KG, 2012. 169 p.
10. Shil`ko T.A. Patogeneticheskie faktory modulyatsii apoptoza mononuklearnykh leykotsitov krovi pri tuberkuleze legkikh: Avtoref. Dis. d-ra med. nauk [Pathogenetic factors modulating apoptosis of blood mononuclear leukocytes blood in pulmonary tuberculosis. Autoref.Doct. med. sci. diss.]. Tomsk, 2009. 44 p.
11. Yarilin A.A. Immunologiya [Immunology]. Moscow, GEOTAR-Media, 2010. 752 p.
12. Agnello D., Lankford C.S., Bream J., Morinobu A., Gadina M., O’Shea J.J., Frucht D.M. Cytokines and Transcription Factors That Regulate T Helper Cell Differentiation: New Players and New Insights. Journal of Clinical Immunology, 2003, vol. 23, no. 3, pp. 147-161.
13. Cooper A.M., Solache A., Khader S.A. Interleukin-12 and tuberculosis: an old story revisited. Current Opinion in Immunology, 2007, vol. 19, no. 4, pp. 441-447.
14. Huber M., Steinwald V., Guralnik A., Br stle A., Kleemann P., Rosenpl nter C., Decker T., Lohoff M. IL-27 inhibits the development of regulatory T cells via STAT3. Int. Immunology, 2008, vol. 20, no. 2, pp. 223-234.
15. Hunter C.A., Kastelein R. Interleukin-27: balancing protective and pathological immunity. Immunity, 2012, vol. 37, no. 6, pp. 960-969.
16. McAleer P.J., Saris C.J., Vella A.T. The WSX-1 pathway restrains intestinal T-cell immunity. Int. Immunol, 2011, vol. 23, no. 2, pp. 129-137.
17. Pompei L., Jang S., Zamlynny B., Ravikumar S., McBride A., Hickman S.P., Salgame P. Disparity in IL-12 release in dendritic cells and macrophages in response to Mycobacterium tuberculosis is due to use of distinct TLRs. J. Immunol, 2007, vol. 178, no. 8, pp. 5192-5199.
18. Robinson C.M., Nau G.J. Interleukin-12 and interleukin-27 regulate macrophage control of Mycobacterium tuberculosis. J. Infect Dis., 2008, vol. 198, no. 3, pp. 359-366.
19. Schwander S., Dheda K. Human lung immunity against Mycobacterium tuberculosis: insights into pathogenesis and protection. Am. J. Respir Crit Care Med, 2011, vol. 183, no. 6, pp. 696-707.
20. Silver J.S., Hunter C.A. Gp130 at the Nexus of Inflammation, Autoimmunity, and Cancer. Journal of leukocyte biology, 2010, vol. 88, no. 6, pp. 1145-1156.
21. Takeda A., Hamano S., Shiraishi H., Yoshimura T., Ogata H., Ishii K. Ishibashi T., Yoshimura A., Yoshida H. WSX-1 over-expression in CD4(+) T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation. Int. Immunol, 2005, vol. 17, no. 7, pp. 889-897.
22. Villarino A.V., Stumhofer J.S., Saris C.J., Kastelein R.A., de Sauvage F.J., Hunter C.A. IL-27 limits IL-2 production during Th1 differentiation. J. Immunol, 2006, vol. 176, no. 1, pp. 237-247.
23. Villarino A.V., Artis D., Bezbradica J.S., Miller O., Saris C.J., Joyce S., Hunter C.A. IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int. Immunol, 2008, vol. 20, no. 6, pp. 739-752.
24. Villarino A.V., Larkin J. 3rd, Saris C.J., Caton A.J., Lucas S., Wong T., de Sauvage F.J., Hunter C.A. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation. J. Immunol, 2005, vol. 174, no. 12, pp. 7684-7691.
25. Watford W.T., Hissong B.D., Bream J.H., Kanno Y., Muul L., O’Shea J.J. Signaling by IL-12 and IL- 23 and the immunoregulatory roles of STAT4. Immunological Reviews, 2004, no. 202, pp. 139-156.
26. Yoshida H., Nakaya M., Miyazaki Y. Interleukin 27: a double-edged sword for offense and defense. J. Leukoc Biol, 2009, vol. 86, no. 6, pp. 1295-1303.
27. Zhao J., Perlman S. Differential effects of IL-12 on Tregs and non-Treg T cells: roles of IFNγ, IL-2 and IL-2R. PLoS One, 2012, vol. 7, no. 9, Mode of access: http://www.ncbi.nlm.nih.gov/pubmed/23029447.
Review
For citations:
Esimova I.E., Urazova O.I., Novitskiy V.V., Khasanova R.R., Filinyuk O.V. SECRETION OF IL-12, IL-27 BY MONONUCLEAR LEUKOCYTES AND EXPRESSION OF THEIR RECEPTORS ON T-LYMPHOCYTES IN CONDITIONS OF DIRECTED CELL INDUCTION IN VITRO IN PULMONARY TUBERCULOSIS. Medical Immunology (Russia). 2014;16(3):237-246. (In Russ.) https://doi.org/10.15789/1563-0625-2014-3-237-246
Views:
1249
Email this article 