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

Mycobacterium 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.

A 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.

The 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.

The 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.