PMID- 16469873
OWN - NLM
STAT- MEDLINE
DCOM- 20060629
LR  - 20210912
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 107
IP  - 11
DP  - 2006 Jun 1
TI  - Uncoupling of T-cell effector functions by inhibitory killer immunoglobulin-like 
      receptors.
PG  - 4449-57
AB  - Killer immunoglobulin-like receptors (KIRs) are a family of regulatory 
      cell-surface molecules expressed on natural killer (NK) cells and memory T-cell 
      subsets. Their ability to prevent the formation of an activation platform and to 
      inhibit NK cell activation is the basis of the missing self model of NK cell 
      function. The benefits of KIR expression for T-cell biology are unclear. We 
      studied how KIR2DL2 regulates T-cell function. Engagement of KIR2DL2 by the 
      ligand human leukocyte antigen (HLA)-Cw3 did not affect conjugate formation 
      between CD4(+)KIR2DL2(+) T cells and superantigen-pulsed target cells or the 
      development of mature immune synapses with lipid rafts. KIR2DL2 and the 
      corresponding HLA-C ligand were initially recruited to the peripheral 
      supramolecular activation cluster (pSMAC). Consequently, KIR2DL2 engagement did 
      not inhibit the phosphorylation of early signaling proteins and T-cell-receptor 
      (TCR)-mediated cytotoxicity or granule exocytosis. After 15-30 minutes, KIR2DL2 
      moved to the central supramolecular activation cluster (cSMAC), colocalizing with 
      CD3. TCR synapses dissociated, and phosphorylated phospholipase C (PLC)-gamma1, 
      Vav1, and extracellular signal-regulated kinase 1/2 (ERK1/2) were reduced 90 
      minutes after stimulation. Gene array studies documented that the inhibition of 
      late signaling events by KIR2DL2 affected transcriptional gene activation. We 
      propose that KIRs on memory T cells operate to uncouple effector functions by 
      modifying the transcriptional profile while leaving granule exocytosis unabated.
FAU - Henel, Gabriella
AU  - Henel G
AD  - Kathleen B. and Mason I Lowance Center for Human Immunology, Emory University 
      School of Medicine, Atlanta, GA 30322, USA.
FAU - Singh, Karnail
AU  - Singh K
FAU - Cui, Dapeng
AU  - Cui D
FAU - Pryshchep, Sergey
AU  - Pryshchep S
FAU - Lee, Won-Woo
AU  - Lee WW
FAU - Weyand, Cornelia M
AU  - Weyand CM
FAU - Goronzy, Jorg J
AU  - Goronzy JJ
LA  - eng
GR  - R01 AG 15043/AG/NIA NIH HHS/United States
GR  - R01 AR 41974/AR/NIAMS NIH HHS/United States
GR  - R01 AI044142/AI/NIAID NIH HHS/United States
GR  - R01 AR041974/AR/NIAMS NIH HHS/United States
GR  - R01 AR 42567/AR/NIAMS NIH HHS/United States
GR  - U19-AI 44142/AI/NIAID NIH HHS/United States
GR  - R01 AG015043/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060209
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (KIR2DL2 protein, human)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR2DL2)
RN  - 0 (Superantigens)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Degranulation
MH  - *Cytotoxicity, Immunologic
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immunologic Memory/immunology
MH  - Membrane Microdomains
MH  - Protein Transport
MH  - Receptors, Immunologic/immunology/*physiology
MH  - Receptors, KIR
MH  - Receptors, KIR2DL2
MH  - Signal Transduction/*immunology
MH  - Superantigens/pharmacology
MH  - T-Lymphocyte Subsets/*immunology
MH  - Transcriptional Activation
PMC - PMC1895796
EDAT- 2006/02/14 09:00
MHDA- 2006/06/30 09:00
PMCR- 2007/06/01
CRDT- 2006/02/14 09:00
PHST- 2006/02/14 09:00 [pubmed]
PHST- 2006/06/30 09:00 [medline]
PHST- 2006/02/14 09:00 [entrez]
PHST- 2007/06/01 00:00 [pmc-release]
AID - S0006-4971(20)64582-7 [pii]
AID - 4449 [pii]
AID - 10.1182/blood-2005-06-2519 [doi]
PST - ppublish
SO  - Blood. 2006 Jun 1;107(11):4449-57. doi: 10.1182/blood-2005-06-2519. Epub 2006 Feb 
      9.