The exhausted CD4CXCR5 T cells involve the pathogenesis of human tuberculosis disease.

OBJECTIVES

CD4CXCR5 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 CD4CXCR5 T cells in human TB.

METHODS

The frequency and function of CD4CXCR5 T cells were evaluated in active TB (ATB) patients and healthy control subjects. The function of CD4CXCR5 T cells was determined after blockade of inhibitory receptors.

RESULTS

The frequency of CD4CXCR5 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 CD4CXCR5 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 CD4CXCR5 T cells. However, blockade of inhibitory receptors Tim-3 and PD-1 not only increased the frequency of CD4CXCR5 T cells, but also restored their proliferation and cytokine secretion potential.

CONCLUSIONS

The increased expression of inhibitory receptors involves the depletion of CD4CXCR5 T cells, and blockade of inhibitory receptors can restore the function of CD4CXCR5 T cells in ATB patients.