The exhausted CD4+CXCR5+ T cells involve the pathogenesis of human tuberculosis disease. (September 2018)

• Record Type: Journal Article
• Authors: Jean Bosco, Munyemana; Wei, Ming; Hou, Hongyan; Yu, Jing; Lin, Qun; Luo, Ying; Sun, Ziyong; Wang, Feng
• Is Part Of: International journal of infectious diseases. Volume 74(2018)
• Page Start: 1
• Page End: 9
• Publication Date: 2018-09
• Subjects: CD4+CXCR5+ T cells -- TB disease -- Inhibitory receptors -- Tim-3 -- PD-1; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2018.06.011
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: The expression of inhibitory receptors Tim-3 and PD-1 on CD4 + CXCR5 + T cells is increased in active TB (ATB) patients. The function of TB-specific CD4 + CXCR5 + T cells is exhausted in ATB patients. Regulation of Tim-3 and PD-1 restores the function of TB-specific CD4 + CXCR5 + T cells. Abstract: 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.