Abstract
BackgroundIt is not fully explained why some active tuberculosis patients show negative interferon-γ release assays (IGRAs). In this study, we tried to explore associations of IGRAs with the characteristics of peripheral Vγ2Vδ2 T cells and their functions of producing cytokines.Methods32 pulmonary tuberculosis patients were enrolled and divided into two groups according to their IGRAs results: 16 with IGRA-negative as test group and 16 with IGRA-positive as control group. Chest X-rays and T-SPOT.TB tests were performed and the severity of the lung lesions was scored. The amount of Vγ2Vδ2T cell and their expression levels of the apoptosis-related membrane surface molecule Fas and FasL in peripheral blood were analyzed by flow cytometry, and the function of secreting cytokines (IFN-γ, TNF-α and IL-17A) of Vγ2Vδ2 T cell were determined by intracellular cytokine staining.ResultsThe IGRA-negative TB patients had more lesion severity scores and displayed reduced peripheral blood Vγ2Vδ2 T cell counts (p = 0.009) as well as higher Fas and FasL expression in peripheral blood Vγ2Vδ2 T cells (p = 0.043, 0.026). A high lesion severity score was correlated with a decreased Vδ2+ T cell number and increased Vγ2Vδ2 T cells Fas/FasL expression leve in the peripheral blood (p = 0.00, P < 0.01). The function of secreting cytokines was slightly impaired in IGRA-negative TB patients (p = 0.402). There is no significant differences in expression levels of Fas and FasL in CD4+ T cells (p = 0.224, 0.287) or CD8+ T cells (p = 0.184, 0.067) between test and control groups.ConclusionCompared with IGRA-positive TB patients, the IGRA-negative TB patients had more lesion severity scores, the number of Vγ2Vδ2 T cells decreased and the function of secreting cytokines impaired. In addition, we suggest that increased expression of Fas/FasL triggers Vγ2Vδ2 T cell apoptosis.
Highlights
It is not fully explained why some active tuberculosis patients show negative interferon-γ release assays (IGRAs)
Some studies using intracellular staining for cytokines suggest that M. tuberculosis (MTB)-activated CD4+ and γδ T-cell secreted large amounts of IFN-γ. γδ T cells have been shown to be more potent producers of IFN-γ than CD4+ T cells [14, 15]. γδ T cells, which account for 1–5% of all peripheral blood T cells [16,17,18] constitute a specific subtype of T cells expressing γδ T cell receptors (TCR) and
Demographic profiles of subjects To explore the relation between IGRAs and Vγ2Vδ2 T cells, we have enrolled two groups of pulmonary tuberculosis patients with IGRAs positive and negative, respectively
Summary
It is not fully explained why some active tuberculosis patients show negative interferon-γ release assays (IGRAs). Interferon-γ release assays (IGRAs) based on the level of IFN-γ secreted by T cells in response to M. tuberculosis (MTB) specific antigens including early secreted antigenic target (ESAT-6) and culture filtrate protein (CFP-10) has higher specificity and sensitivity than the conventional tuberculin skin test (TST) [3, 4]. These specific antigens are present in the genome of MTB and absent in. Some active pulmonary tuberculosis patients exhibit an decreased ability of Vγ2Vδ2+ T cells to generate IFN-γ in response to phosphor-antigens [27, 28]. We have found that anergic pulmonary tuberculosis is accompanied by reduced Vγ2Vδ2 T cell percentage, and elevated Vγ2Vδ2 cell FasL expression [32]
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