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

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.