NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions: role in the NK cell-mediated negative regulation of T cell responses.

Alessandra Zingoni (1) , Michele Ardolino (1) , Angela Santoni (1, 2) , Cristina Cerboni (1)

1 Department of Molecular Medicine
2 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo

The negative regulation of adaptive immunity is relevant to maintain lymphocyte homeostasis. Several studies on natural killer (NK) cells have shown a previously unappreciated immunomodulatory role, as they can negatively regulate T cell-mediated immune responses by direct killing and by secretion of inhibitory cytokines. The molecular mechanisms of T cell suppression by NK cells, however, remained elusive. Only in the last few years has it become evident that, upon activation, human T cells express MICA-B, ULBP1-3, and PVR, ligands of the activating receptors NKG2D and DNAM-1, respectively. Their expression renders T cells targets of NK cell lysis, representing a new mechanism taking part to the negative regulation of T cell responses. Studies on the expression of NKG2D and DNAM-1 ligands on T cells have also contributed in understanding that the activation of ATM (ataxia-telangiectasia, mutated)/ATR (ATM/Rad3-related) kinases and the DNA damage response is a common pathway regulating the expression of activating ligands in different types of cells and under different conditions. The functional consequences of NKG2D and DNAM-1 ligand expression on activated T cells are discussed in the context of physiologic and pathologic processes such as infections, autoimmunity, and graft versus host disease.

Domains: Immunology

Alessandra Zingoni, Michele Ardolino, Angela Santoni, Cristina Cerboni. NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions: role in the NK cell-mediated negative regulation of T cell responses.. Frontiers in Immunology, 2012, 3, pp.408. ⟨10.3389/fimmu.2012.00408⟩. ⟨pasteur-00966878⟩