Abstract
Although the efficacy of tuberculosis (TB) vaccines is tightly linked to cell-mediated immunity, some functions of T and B cells in TB patients remain unclear. To address how Mycobacterium tuberculosis infection inhibits T effector responses, we assessed the proportions of T cell subsets and B cells in peripheral blood from pulmonary TB (PTB) patients, pleural TB (PLTB) patients, and healthy subjects (HS, who showed purified protein derivative (PPD)-positive reactions) with flow cytometry. Compared to HS, PTB and PLTB patients exhibited higher proportions of B cells and Th17 cells, and lower proportions of Th2 cells and ratios of Th1 to Th17 cells and of Th2 to Th17 cells. PTB patients had higher CD4+ T cells and PD-1+ CD4+ T cells than HS. Newly diagnosed PTB patients (nPTB) had higher proportions of B cells than HS; in contrast, PTB patients subjected to effective treatments (oPTB) and HS shared similar proportions of B cells. oPTB patients had higher proportions of CD4+ T cells, Th17 cells, and PD-1+ CD4+ T cells than HS, but this difference did not occur in nPTB patients. These findings suggest that shifting ratios of Th1 to Th17 cells may be beneficial for M. tuberculosis to amplify.
Highlights
Tuberculosis (TB), a serious infectious disease caused by Mycobacterium tuberculosis, is currently leading to the deaths of about 1.7 million people and yielding millions of new TB cases per year [1]
pulmonary TB (PTB) and pleural TB (PLTB) patients had a higher percentage of CD3− CD19+ lymphocyte (B cells) than healthy subjects (HS) (p = 0.0003 and p = 0.049), and there was no difference in the percentage of B cells between PTB and PLTB patients (p > 0.05) (Figure 1(a)). Newly diagnosed PTB patients (nPTB) and cPTB patients had a higher percentage of B cells than HS (p = 0.000 and p = 0.001), and oPTB patients exhibited similar percentages of B cells with nPTB patients, cPTB patients, and HS
There were no differences in the proportions of CD3+ T cells among nPTB, oPTB, cPTB patients, and HS. nPTB and oPTB patients had higher percentages of CD4+ T cells than HS (p = 0.040 and p = 0.027), and this phenomenon did not appear in nPTB, oPTB, and cPTB patients; oPTB patients (a) had a lower percentage of CD8+ T cells than HS (p = 0.037) whereas nPTB patients, cPTB patients, and HS shared similar percentages of CD8+ T cells (Figure 2(b))
Summary
Tuberculosis (TB), a serious infectious disease caused by Mycobacterium tuberculosis, is currently leading to the deaths of about 1.7 million people and yielding millions of new TB cases per year [1]. Today available vaccines are able to induce long-lived antibody responses, but vaccines against intracellular organisms that require cell-mediated immunity (CMI) are neither available nor uniformly effective [2]. Mycobacterium bovis Bacille Calmette-Guérin (BCG) is a vaccine against M. tuberculosis, but it lacks longevity of protection and is not effective enough to stop TB spreading. It is needed to develop novel TB vaccines based on the mechanisms underlying protective immunity against M. tuberculosis. CMI plays a pivotal role in controlling M. tuberculosis infection [3]. The cellular immune response to intracellular pathogens comprises a spectrum of T-cell subpopulations characterized by distinct cytokine secretion profiles and cell surface marker phenotypes [4]. Th1, Th2, and Th17 cells are characterized by the production of different patterns of cytokines [5], and follicular helper CD4 T (Tfh) cells differ from Th1, Th2 or Th17 cells in gene expression and developmental regulation [6]
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