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The exhausted CD4+CXCR5+ T cells involve the pathogenesis of human tuberculosis disease
Munyemana Jean Bosco1, Ming Wei2, Hongyan Hou1
1Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.
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