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.

Highlights

  • Инфекция и иммунитет гулируя функциональную активность широкого спектра клеток врожденного и приобретенного иммунитета

  • Eradication of an intracellular pathogen M. tuberculosis requires to induce a Th1 response by activating IFNγ-producing tissue macrophages

  • able to secrete a broad range of cytokines

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Summary

Introduction

Инфекция и иммунитет гулируя функциональную активность широкого спектра клеток врожденного и приобретенного иммунитета. Относительное содержание CD3+CD4+ клеток в рамках общей популяции Т-лимфоцитов периферической крови достоверно не различалось (р = 0,275) между группами и составляло 63,03% (58,65; 68,80) у больных ТБ и 64,32% (61,19; 71,29) в группе сравнения. Вместе с тем было показано, что у больных ТБ достоверно снижалось процентное содержание СМ Th клеток по сравнению с группой контроля (25,15% (19,63; 36,20) и 34,27% (30,40; 48,93) соответственно, при р = 0,002).

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