Blood 2007,
PMID: 17405908
Cerboni, Cristina; Zingoni, Alessandra; Cippitelli, Marco; Piccoli, Mario; Frati, Luigi; Santoni, Angela
Recent evidence indicates that natural killer (NK) cells can negatively regulate T-cell responses, but the mechanisms behind this phenomenon as a consequence of NK-T-cell interactions are poorly understood. We studied the interaction between the NKG2D receptor and its ligands (NKG2DLs), and asked whether T cells expressed NKG2DLs in response to superantigen, alloantigen, or a specific antigenic peptide, and if this rendered them susceptible to NK lysis. As evaluated by FACS, the major histocompatibility complex (MHC) class I chain-related protein A (MICA) was the ligand expressed earlier on both CD4(+) and CD8(+) T cells in 90% of the donors tested, while UL16-binding protein-1 (ULBP)1, ULBP2, and ULBP3 were induced at later times in 55%-75% of the donors. By carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling, we observed that NKG2DLs were expressed mainly on T cells that had gone through at least one division. Real-time reverse-transcription polymerase chain reaction confirmed the expression of all NKG2DLs, except ULBP4. In addition, T-cell activation stimulated phosphorylation of ataxia-telangiectasia mutated (ATM), a kinase required for NKG2DLs expression after DNA damage, and ATM/Rad3-related kinase (ATR) inhibitors blocked MICA induction on T cells with a mechanism involving NF-kappaB. Finally, we demonstrated that activated T cells became susceptible to autologous NK lysis via NKG2D/NKG2DLs interaction and granule exocytosis, suggesting that NK lysis of T lymphocytes via NKG2D may be an additional mechanism to limit T-cell responses.
Diseases/Pathways annotated by Medline MESH: Autolysis
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Text Mining Data
NKG2D — ATM/ATR: "
Antigen activated human T lymphocytes express cell-surface
NKG2D ligands via an
ATM/ATR dependent mechanism and become susceptible to autologous NK- cell lysis
"
MICA → ATM/Rad3 related kinase (ATR): "
In addition, T-cell activation stimulated phosphorylation of ataxia-telangiectasia mutated (ATM), a kinase required for NKG2DLs expression after DNA damage, and ATM/Rad3 related kinase (ATR) inhibitors blocked MICA induction on T cells with a mechanism involving NF-kappaB
"
ataxia-telangiectasia mutated (ATM) → ATM/Rad3 related kinase (ATR): "
In addition, T-cell activation stimulated phosphorylation of ataxia-telangiectasia mutated (ATM) , a kinase required for NKG2DLs expression after DNA damage, and ATM/Rad3 related kinase (ATR) inhibitors blocked MICA induction on T cells with a mechanism involving NF-kappaB
"
Manually curated Databases
No curated data.