The exhausted CD4⁺CXCR5⁺ T cells involve the pathogenesis of human tuberculosis disease

Objectives CD4 + CXCR5 + T cells have previously been established. However, their decreased frequency during tuberculosis (TB) disease is only partially understood. The aim of this study was to explore the depletion of CD4 + CXCR5 + T cells in human TB. Methods The frequency and function of CD4 + CXCR5 + T cells were evaluated in active TB (ATB) patients and healthy control subjects. The function of CD4 + CXCR5 + T cells was determined after blockade of inhibitory receptors. Results The frequency of CD4 + CXCR5 + T cells was decreased in ATB patients. The expression of activation markers (HLA-DR and ICOS) and inhibitory receptors (Tim-3 and PD-1) on CD4 + CXCR5 + T cells was increased in the ATB group. TB-specific antigen stimulation induced higher expression of inhibitory receptors than phytohemagglutinin stimulation in the ATB group. In contrast, TB antigen stimulation did not induce a significantly increased expression of IL-21 and Ki-67 on CD4 + CXCR5 + T cells. However, blockade of inhibitory receptors Tim-3 and PD-1 not only increased the frequency of CD4 + CXCR5 + T cells, but also restored their proliferation and cytokine secretion potential. Conclusions The increased expression of inhibitory receptors involves the depletion of CD4 + CXCR5 + T cells, and blockade of inhibitory receptors can restore the function of CD4 + CXCR5 + T cells in ATB patients.