Mechanisms of Vδ1 γδ T Cell Activation by Microbial Components

Abstract

There are two major subsets of γδ T cell in humans. Vγ2Vδ2 T cells predominate in the circulation and significantly expand in vivo during a variety of infectious diseases. Ags identified for the Vδ2 T cells are nonpeptide phosphate, amine, and aminobisphosphonate compounds. In contrast, Vδ1-encoded TCRs account for the vast majority of γδ T cells in tissues such as intestine and spleen. Some of these T cells recognize CD1c and MHC class I-related chain B molecules. These T cells are cytotoxic and use both perforin- and Fas-mediated cytotoxicity. A fundamental question is how these γδ T cells are activated during microbial exposure to carry out effector functions. In this study, we provide evidence for a mechanism by which Vδ1 γδ T cells are activated by inflammatory cytokines in the context of the Vδ1 TCR. Dendritic cells are necessary as accessory cells for microbial Ag-mediated Vδ1 γδ T cell activation. Cytokine (IL-12), adhesion (LFA3/CD2, LFA1/ICAM1) and costimulatory (MHC class I-related chain B molecule/NK-activating receptor G2D) molecules play a significant role along with Vδ1 TCR in this activation.