PMID- 23440333
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130227
LR  - 20211021
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 4
DP  - 2013
TI  - Donor killer immunoglobulin-like receptor genes and reactivation of 
      cytomegalovirus after HLA-matched hematopoietic stem-cell transplantation: HLA-C 
      allotype is an essential cofactor.
PG  - 36
LID - 10.3389/fimmu.2013.00036 [doi]
LID - 36
AB  - Natural killer (NK) cells whose killer immunoglobulin-like receptors (KIRs) 
      recognize human leukocyte antigen (HLA) ligand are "licensed" for activity. In 
      contrast, non-licensed NK cells display KIRs for which ligand is absent from the 
      self genotype and are usually hyporesponsive. Surprisingly, non-licensed cells 
      are active in tumor control after hematopoietic stem-cell transplantation (HSCT) 
      and dominate NK response to murine cytomegalovirus (CMV) infection. From those 
      reports, we hypothesized that control of human CMV early after HSCT is influenced 
      by donor KIR genes whose HLA ligand is absent-from-genotype of HLA-matched donor 
      and recipient. To investigate, we studied CMV reactivation through Day 100 after 
      grafts involving CMV-seropositive donor and/or recipient. A multivariate 
      proportional rates model controlled for variability in surveillance and 
      established covariates including acute graft-versus-host disease; statistical 
      significance was adjusted for testing of multiple KIRs with identified HLA class 
      I ligand (2DL1, 2DL2/3, 2DS1, 2DS2, full-length 2DS4, 3DL1/3DS1, 3DL2). Among 
      HSCT recipients (n = 286), CMV reactivation-free survival time varied with 
      individual donor KIR genes evolutionarily specific for HLA-C: when ligand was 
      absent from the donor/recipient genotype, inhibitory KIRs 2DL2 (P < 0.0001) and 
      2DL1 (P = 0.015) each predicted inferior outcome, and activating KIRs 2DS2 (P < 
      0.0001), 2DS1 (P = 0.016), and 2DS4 (P = 0.016) each predicted superior outcome. 
      Otherwise, with ligand present-in-genotype, donor KIR genes had no effect. In 
      conclusion, early after HLA-matched HSCT, individual inhibitory and activating 
      KIR genes have qualitatively different effects on risk of CMV reactivation; 
      unexpectedly, absence of HLA-C ligand from the donor/recipient genotype 
      constitutes an essential cofactor in these associations. Being KIR- and 
      HLA-C-specific, these findings are independent of licensing via alternate NK cell 
      receptors (NKG2A, NKG2C) that recognize HLA-E.
FAU - Behrendt, Carolyn E
AU  - Behrendt CE
AD  - Division of Biostatistics and Epidemiology, City of Hope Duarte, CA, USA.
FAU - Nakamura, Ryotaro
AU  - Nakamura R
FAU - Forman, Stephen J
AU  - Forman SJ
FAU - Zaia, John A
AU  - Zaia JA
LA  - eng
GR  - R01 AI058148/AI/NIAID NIH HHS/United States
GR  - M01 RR000043/RR/NCRR NIH HHS/United States
GR  - P30 CA033572/CA/NCI NIH HHS/United States
GR  - R01 CA145207/CA/NCI NIH HHS/United States
GR  - P01 CA030206/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20130221
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC3578282
OTO - NOTNLM
OT  - HLA
OT  - cytomegalovirus, hematopoietic stem-cell transplantation
OT  - killer Ig-like receptors
OT  - natural killer cells
EDAT- 2013/02/27 06:00
MHDA- 2013/02/27 06:01
PMCR- 2013/01/01
CRDT- 2013/02/27 06:00
PHST- 2012/11/06 00:00 [received]
PHST- 2013/01/30 00:00 [accepted]
PHST- 2013/02/27 06:00 [entrez]
PHST- 2013/02/27 06:00 [pubmed]
PHST- 2013/02/27 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2013.00036 [doi]
PST - epublish
SO  - Front Immunol. 2013 Feb 21;4:36. doi: 10.3389/fimmu.2013.00036. eCollection 2013.