THE ROLE OF VIOLATIONS IN THE CYTOKINES SYTEM OF THE INTERLEUKIN 12 FAMILY AND THEIR RECEPTORS IN IMMUNOPATHOGENESIS OF TUBERCULOSIS

O.I. Urazova, I.E. Esimova, R.R. Khasanova, V.V. Novitsky, E.G. Churina, T.E. Kononova
Siberian State Medical University, Russian Federation, 634050, Tomsk, Moscowsky trakt, 2

Introduction. Disorders in anti-TB immunity may be formed at the stage of interaction between antigen-presenting cells and T-lymphocytes by means of cytokines and their receptors. The key cytokines of T-lymphocyte activation are interleukins (IL) of the IL12 family. The disorder in intracellular transduction of signals which are generated in the process of cell-cell interaction may also be the factor of the immune response dysfunction at the stage of T-lymphocyte activation. The aim of the study. To analyze the role of disorders in IL12 family cytokine secretion, expression of their receptors and intracellular transduction of T-lymphocyte activation signals related to them in immunopathogenesis of tuberculosis. Methods. The evaluation of basal and induced IL12 and IL27 secretion by mononuclear leukocytes in vitro along with the concentration of phosphorylated forms of tyrosine kinases (Jak1, Jak2, Tyk2) and transcription factors (STAT1, STAT4), participating in transduction of the signal of IL12-mediated T cell activation, in blood lymphocyte lysates was carried out with the use of ELISA. The expression of receptors to IL12 and IL27 on T lymphocytes was estimated with the use of flow cytometry. The clinical form of TB and drug resistance of the infectious agent were taken into account in the analysis of the research results. Results. The level of IL12 secretion in TB patients has been found to vary, with more marked hyposecretion of the cytokine in the infiltrative form of the disease, and due to the expansion of the range of M. tuberculosis drug resistance. In the meantime, hyposecretion of IL12 is associated with the overexpression of hypoexpressio β2 receptor subunit to IL12 and gp130 receptor subunit to IL27 – the cytokine which promotes the binding of IL12 to T-lymphocyte. These disorders are accompanied by the deficit of active forms of tyrosine kinases and transcription factors of JAK/STAT-signaling pathway in T-lymphocytes, which prevents the realization of the intracellular IL12-dependent pathway, mediating the T cell activation. Conclusion. Dysregulation of anti-TB immune response at the stage of its triggering is associated with the hyposecretion of IL12, the deficit in receptors to the IL12 family cytokines on T-lymphocytes as well as T cell molecules which participate in transduction of the signal of IL12-dependent T-lymphocyte activation.
Keywords: 
IL12, IL27, signal transduction, T-lymphocytes, tuberculosis