Human Vγ9Vδ2 T cells play a crucial role in early immune response to intracellular pathogens. Their number is drastically increased in the peripheral blood of patients during the acute phase of brucellosis. In vitro, Vγ9Vδ2 T cells exhibit strong cytolytic activity against Brucella-infected cells and impair intracellular growth of Brucella suis in autologous macrophages. Vγ9Vδ2 T cells use cell contact-dependent mechanisms such as the release of lytic granules and Fas-mediated signals to lyse infected macrophages and decrease the development of intracellular Brucella. Although the involvement of the T-cell receptor (TCR) in the triggering of these responses is known, other surface receptors can modulate Vγ9Vδ2 T-cell response. In this study, we have investigated a potential role of NKG2D and its ligands in the anti-infectious activity of human Vγ9Vδ2 T cells against B. suis. We show that the recruitment of NKG2D by its ligands is sufficient to induce cytokine production and the release of lytic granules through PI3K-dependent pathways, but can also increase the TCR-triggered responses of Vγ9Vδ2 T cells. We also demonstrate that the interaction between NKG2D and its main ligand expressed on Brucella-infected macrophages, UL16-binding protein 1 (ULBP1), is involved in the inhibition of bacterium development. Altogether, these results suggest a direct contribution of NKG2D and its ligands to the anti-infectious activity of Vγ9Vδ2 T cells.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.