Abstract
ObjectiveTo study the association of anergic pulmonary tuberculosis with Vδ2+ T cells and related cytokine levels.Methods82 pulmonary tuberculosis patients were divided into two groups according to their purified protein derivative tuberculin skin test (TST) results: 39 with TST-negative anergic pulmonary tuberculosis and 43 with TST-positive pulmonary tuberculosis, while 40 healthy volunteers were used as control. Based on chest X-ray results, the tuberculosis lesions were scored according to their severity, with a score of ≤ 2.5 ranking as mild, 2.5-6 as moderate and ≥ 6 as severe. The Vδ2+ T cell percentage and their expression levels of the apoptosis-related membrane surface molecule FasL in peripheral blood and bronchoalveolar lavage fluids (BALF) were analyzed by flow cytometry, while IL-2, IL-4, IL-6 and IL-10 cytokine and γ-interferon (γ-IFN) concentrations in peripheral blood were determined by ELISA.ResultsMost of the patients with chest X-ray lesion scores higher than 6 belonged to the anergic tuberculosis group (P<0.05). Anergic pulmonary tuberculosis patients displayed reduced peripheral blood Vδ2+ T cell counts (P<0.05) and higher FasL expression in peripheral blood Vδ2 + T cells (P <0.05). The Vδ2+ T cell percentages in the BALF of all tuberculosis patients were lower than in their peripheral blood (P <0.05), and IL-4 and IL-10 concentrations in peripheral blood of anergic tuberculosis patients were higher than in TST-positive tuberculosis patients and healthy controls (P <0.05).ConclusionAnergic pulmonary tuberculosis is accompanied by reduced Vδ2+ T cell percentage, and elevated Vδ2+ T cell FasL expression as well as enhanced IL-4 and IL-10 levels in peripheral blood.
Highlights
Tuberculosis has the greatest mortality rate among all infectious diseases, which is mainly due to the current lack of effective protective vaccines and incomplete understanding of the mechanisms by which M. tuberculosis escapes immune surveillance [1,2]
Since the respiratory epithelium mucosa and alveolar surface are the first places through which M. tuberculosis invades the host, Vδ2+ T cells might serve as a part of the firstline host immune defense against tuberculosis infections
It has been reported that reduction of Vδ2+ T cells in anergic tuberculosis patients is due to the inhibitory effects of regulatory T cells or dysregulation of Vδ2+ T cell functions [15,16,17]
Summary
Tuberculosis has the greatest mortality rate among all infectious diseases, which is mainly due to the current lack of effective protective vaccines and incomplete understanding of the mechanisms by which M. tuberculosis escapes immune surveillance [1,2]. One subtype is anergic tuberculosis, with negative TST results; more accurately, anergic tuberculosis, which accounts for about 15% of tuberculosis cases, refers to a disease that is negative for tuberculin purified protein derivative skin tests without a concomitant immunodeficiency disease. These patients often do not display granuloma formation, yet have severe atypical clinical manifestations [3]. The present study sought to further explore associations of anergic tuberculosis with Vδ2+ T cell percentages and serum concentrations of related cytokines in order to elucidate factors affecting immunological damage and protection, and to further characterize anti-tuberculosis defense mechanisms, thereby providing the basis for optimized chemotherapy regimens and immunological therapies as well as for designing new vaccines against tuberculosis [13,14]
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