Mycobacterium tuberculosis-specific memory T cells in bronchoalveolar lavage of patients with pulmonary tuberculosis

Abstract

BackgroundMycobacterium tuberculosis(MTB) most often infects the lungs and results in pulmonary tuberculosis(TB). MTB-specific memory T cells are able to respond quickly against antigens and help reduce the burden of pulmonary bacteria. The characteristics, function and chemotaxis axis of memory T cells in the lung remain unclear. The current study aimed to clarify the classification, function and recruitment of local antigen-specific memory T cells in the lung and the periphery blood of patients with pulmonary TB. MethodsA total of 85 patients with active pulmonary TB were included in the study. Bronchoalveolar lavage fluid (BALF) and Peripheral blood were collected for further detection. The cell-surface markers and intracellular staining of memory T cell subtypes were measured by flow cytometry. The level of CXCL9, CXCL10 and CXCL11 in Bronchoalveolar lavage fluid cells and peripheral blood mononuclear cells (PBMC) were measured by Real-time PCR. ResultsThe ratio of effective Memory T cells (TEM) were the highest in BALF of patients with pulmonary TB. In patients, CXCR3 and its ligands was increased in memory T cells of BALF compared with PBMC. IFN-γ+TNF-α+ effective Memory T cells and central memory T cells from BALF were increased after antigen stimulation. CXCR3 was higher in IFN-γ+ compared with IFN-γ− in CD4+ TCM and TEM from BALF of patients. Compared with PBMC, the PD-1 levels of terminal effector memory RA+(TEMRA) and TEM cells in CD4+ memory T cells of BALF were significantly increased. In addition, PD-1 was increased in IFN-γ+ compared with IFN-γ− in CD4+TEM from BALF of patients. There was no difference in Treg ratio between PBMC and BALF of TB patients. ConclusionsThe CXCL9/CXCL11-CXCR3 axis may participate in the chemotaxis of memory T cells from the peripheral to lung. CD4+TEM and TEMRA in BALF may have exhausted, especially the cytokine producing TEM. Our study clarified the characteristics of antigen-specific memory T cells in local lung and may have impact on strategies of therapy and vaccine.