TY - JOUR
T1 - NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions
T2 - Role in the NK cell-mediated negative regulation of T cell responses
AU - Zingoni, Alessandra
AU - Ardolino, Michele
AU - Santoni, Angela
AU - Cerboni, Cristina
PY - 2012
Y1 - 2012
N2 - The negative regulation of adaptive immunity is relevant to maintain lymphocyte home-ostasis. 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, humanT 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 activatedT cells are discussed in the context of physiologic and pathologic processes such as infections, autoimmunity, and graft versus host disease.
AB - The negative regulation of adaptive immunity is relevant to maintain lymphocyte home-ostasis. 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, humanT 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 activatedT cells are discussed in the context of physiologic and pathologic processes such as infections, autoimmunity, and graft versus host disease.
KW - Cell proliferation
KW - DNA damage response
KW - DNAM-1 ligands
KW - NK-T cell cross-talk
KW - NKG2D ligands
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U2 - 10.3389/fimmu.2012.00408
DO - 10.3389/fimmu.2012.00408
M3 - Article
C2 - 23316196
AN - SCOPUS:84874232157
VL - 3
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - JAN
M1 - Article 408
ER -