Altered peripheral blood Th17 and follicular T-helper subsets in patients with pulmonary tuberculosis

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Abstract

Tuberculosis (TB) is one of the most common infections worldwide. Eradication of an intracellular pathogen M. tuberculosis requires to induce a Th1 response by activating IFNγ-producing tissue macrophages. Along with Th1 cells, various subsets of Th17 and follicular T-helper cells (Tfh) able to secrete a broad range of cytokines, including IFNγ, can also be involved in eliminating bacterial pathogens. It justified analyzing in this study changes in percentage of various peripheral blood Th subsets, including Th1, Th2, Th17 and Tfh cells, in TB patients. For this, major CD3+CD4+ T cell subsets were assessed by using multicolor flow cytometry in TB patients (n = 40) and healthy volunteers (n = 30). It was found that in TB patients vs. control group percentage of peripheral blood CD45RA–CCR7+ central memory (CM) Th was decreased also affecting frequency of some functional T cell subsets, e.g. either lowering Th2 cells (9.11% (6.95; 13.77) vs. 7.21% (5.64; 9.84), p = 0.012) or elevating CCR6+ Th17 subsets (35.92% (27.72; 41.06) vs. 40.39% (35.41; 47.79; p = 0.016), respectively, but not influencing Th1 and Tfh subsets frequencies. Moreover, percentage of total CCR6+ CM Th cells in TB patients vs. control was decreased in CCR4–CXCR3+ Th17.1 cell subset (42.87% (33.64; 49.45) vs. 52.26% (46.45; 56.95), p < 0.001), whereas standard CCR4+CXCR3– Th17 and CCR6+ DP Th17 subsets were elevated (p = 0.005 and p = 0.002, respectively). In addition, altered Tfh subset composition associated with the increased (p = 0.021) percentage of CXCR3–CCR6– Tfh2 cells, but decreased CXCR3+CCR6– Tfh1 cells (p = 0.036) was observed. Finally, frequency of peripheral blood Th subsets noted above was also analyzed within effector memory (CD45RA–CCR7–) cells. It was found that in TB patients vs. volunteers frequency of Th17.1 cells was also significantly lower (p = 0.006) in CCR6+ EM Th (54.43% (41.19; 91.92) vs. 61.76% (54.01; 65.63), whereas percentage of double-positive Th17 was significantly increased (20.83% (15.12; 30.87) and 12.93 % (9.80; 19.01), respectively, p < 0.001). Thus, it suggests that during M. tuberculosis infection percentage of IFNγ-producing Th17 and Tfh cells was reduced compared to control group also affecting both central memory Th cells patrolling peripheral lymphoid organs as well as effector memory Th cells able to exit to site of infection. 

About the authors

I. V. Kudryavtsev

St. Petersburg State University;
Institute of Experimental Medicine;
Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: igorek1981@yandex.ru

Kudryavtsev Igor Vladimirovich., PhD (Biology), Senior Researcher, Laboratory of Immunology, Institute of Experimental Medicine; Associate Professor, Department of Immunology, Pavlov First St. Petersburg State Medical University

Russian Federation

M. K Serebriakova

Institute of Experimental Medicine

Email: m-serebryakova@yandex.ru
Serebriakova Maria Konstantinovna, Researcher, Department of Immunology Russian Federation

A. A. Starshinova

St. Petersburg State University

Email: starshinova_777@mail.ru
Starshinova Anna Andreevna, PhD, MD (Medicine), Leading Researcher, Autoimmunity Mosaic Laboratory Russian Federation

Yu. S. Zinchenko

St. Petersburg State University;
St. Petersburg Research Institute of Phthisiopulmonology

Email: ulia-zinchenko@yandex.ru
Zinchenko Yulia Sergeevna, Junior Researcher, Autoimmunity Mosaic Laboratory, St. Petersburg State University; Junior Researcher, Research Institute of Phthisiopulmonology Russian Federation

N. Yu. Basantsova

St. Petersburg State University;
St. Petersburg Research Institute of Phthisiopulmonology

Email: fromrussiawithlove_nb@mail.ru
Basantsova Natalia Yuryevna, Junior Researcher, Autoimmunity Mosaic Laboratory, Assistant Professor, Department of Faculty Therapy, St. Petersburg State University; Junior Researcher, Research Institute of Phthisiopulmonology Russian Federation

E. N. Belyaeva

"St. Petersburg Research Institute of Phthisiopulmonology" of the Ministry of Health of the Russian Federation; St. Petersburg City hospital №2

Email: starshinova_777@mail.ru
Belyaeva Ekatherine Nikolaevna, PhD (Medicine), Junior Researcher, Research Institute of Phthisiopulmonology; Head of the Department St. Petersburg City Hospital No. 2 Russian Federation

M. V. Pavlova

St. Petersburg Research Institute of Phthisiopulmonology" of the Ministry of Health of the Russian Federation

Email: starshinova_777@mail.ru
Pavlova Maria Vasil’evna, PhD, MD (Medicine), Professor, Leading Researcher, Head of Research Direction “Phthisiopulmonology” ulmonology Russian Federation

P. K. Yablonskiy

St. Petersburg State University;
St. Petersburg Research Institute of Phthisiopulmonology

Email: piotr_yablonskii@mail.ru
Yablonskii Peter Kazimirovich, PhD, MD (Medicine), Professor, Dean of the Medicine Faculty, St. Petersburg State University; Director of the Research Institute of Phthisiopulmonology Russian Federation

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Copyright (c) 2019 Kudryavtsev I.V., Serebriakova M.K., Starshinova A.A., Zinchenko Y.S., Basantsova N.Y., Belyaeva E.N., Pavlova M.V., Yablonskiy P.K.

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