Activation and Regulation of Blood Vδ2 T Cells Are Amplified by TREM-1+ during Active Pulmonary Tuberculosis

活动性肺结核期间 TREM-1+ 扩增血液 Vδ2 T 细胞的激活和调节

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作者:Yongjian Wu, Yin-Min Fang, Li Ding, Xi Liu, Ngiambudulu M Francisco, Jinsheng Wen, Chunxin Liao, Zhiming Ma, Zi Li, Miao Li, Siqi Ming, Ting Liu, Mei Zhang, Minhao Wu, Muazzam Jacobs, Sitang Gong, Xi Huang

Abstract

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a receptor mainly expressed on myeloid cells, and it plays an important role in modulating immune response against infectious agents. The function of TREM-1 on nonmyeloid cells such as Vδ2 T cells has not been characterized, and their role in pulmonary tuberculosis (TB) remains unclear. To assess the expression of TREM-1 on blood Vδ2 T cells from pulmonary TB patients and investigate its mechanism of induction, we exploited flow cytometry analysis to study the expression of TREM-1 on Vδ2 T cells from active pulmonary TB patients and control subjects. In this study we demonstrate that TREM-1 (TREM-1+) is highly expressed on Vδ2 T cells of patients with active pulmonary TB. Unlike TREM-1--expressing Vδ2 T cells, TREM-1+-producing Vδ2 T cells display APC-like phenotypes. Surprisingly, TREM-1+ signaling promotes the Ag-presenting capability of Vδ2 T cells to induce the CD4+ T cell response. TREM-1+Vδ2 T cells induced the proliferation and differentiation of naive CD4+ T cells, as well as the elimination of intracellular mycobacteria. We identified TREM-1+ (but not TREM-1-) as an Ag-presentation amplifier on human blood Vδ2 T cells, and data shed new light on the regulation of Vδ2 T cells in the phase of innate and adaptive immune responses against Mycobacterium tuberculosis infection. Targeting TREM-1+Vδ2 T cells may be a promising approach for TB therapy.

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