Profile of Mycobacterium tuberculosis-specific CD4 T cells at the site of disease and blood in pericardial tuberculosis

Abstract

ABSTRACTOur understanding of the immune response at the site of disease in extra-pulmonary tuberculosis (EPTB) is still limited. In this study, using flow cytometry, we defined the pericardial fluid (PCF) cellular composition and compared the phenotypic and functional profile of Mycobacterium tuberculosis (Mtb)-specific T cells between PCF and whole blood in 16 patients with pericardial TB (PCTB). We found that lymphocytes were the predominant cell type in PCF in PCTB, with a preferential influx of CD4 T cells. The frequencies of TNF-α producing myeloid cells and Mtb-specific T cells were significantly higher in PCF compared to blood. Mtb-specific CD4 T cells in PCF exhibited a distinct phenotype compared to those in blood, with greater GrB expression and lower CD27 and KLRG1 expression. We observed no difference in the production IFNγ, TNF or IL-2 by Mtb-specific CD4 T cells between the two compartments, but MIP-1β production was lower in the PCF T cells. Bacterial loads in the PCF did not relate to the phenotype or function of Mtb-specific CD4 T cells. Upon anti-tubercular treatment completion, HLA-DR, Ki-67 and GrB expression was significantly decreased, and relative IL-2 production was increased in peripheral Mtb-specific CD4 T cells. Overall, using a novel and rapid experimental approach to measure T cell response ex vivo at site of disease, these results provide novel insight into molecular mechanisms and immunopathology at site of TB infection of the pericardium.