PMID- 18945967
OWN - NLM
STAT- MEDLINE
DCOM- 20090501
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 113
IP  - 13
DP  - 2009 Mar 26
TI  - Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched 
      haploidentical HSCT for pediatric patients: evaluation of the functional role of 
      activating KIR and redefinition of inhibitory KIR specificity.
PG  - 3119-29
LID - 10.1182/blood-2008-06-164103 [doi]
AB  - We analyzed 21 children with leukemia receiving haploidentical hematopoietic stem 
      cell transplantation (haplo-HSCT) from killer immunoglobulin (Ig)-like receptors 
      (KIR) ligand-mismatched donors. We showed that, in most transplantation patients, 
      variable proportions of donor-derived alloreactive natural killer (NK) cells 
      displaying anti-leukemia activity were generated and maintained even late after 
      transplantation. This was assessed through analysis of donor KIR genotype, as 
      well as through phenotypic and functional analyses of NK cells, both at the 
      polyclonal and clonal level. Donor-derived KIR2DL1(+) NK cells isolated from the 
      recipient displayed the expected capability of selectively killing C1/C1 target 
      cells, including patient leukemia blasts. Differently, KIR2DL2/3(+) NK cells 
      displayed poor alloreactivity against leukemia cells carrying human leukocyte 
      antigen (HLA) alleles belonging to C2 group. Unexpectedly, this was due to 
      recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and 
      by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, 
      C2/C2 leukemia blasts were killed by KIR2DL2/3(+) (or by NKG2A(+)) NK cells that 
      coexpressed KIR2DS1. This could be explained by the ability of KIR2DS1 to 
      directly recognize C2 on leukemia cells. A role of the KIR2DS2 activating 
      receptor in leukemia cell lysis could not be demonstrated. Altogether, these 
      results may have important clinical implications for the selection of optimal 
      donors for haplo-HSCT.
FAU - Pende, Daniela
AU  - Pende D
AD  - Immunologia, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 
      daniela.pende@istge.it
FAU - Marcenaro, Stefania
AU  - Marcenaro S
FAU - Falco, Michela
AU  - Falco M
FAU - Martini, Stefania
AU  - Martini S
FAU - Bernardo, Maria Ester
AU  - Bernardo ME
FAU - Montagna, Daniela
AU  - Montagna D
FAU - Romeo, Elisa
AU  - Romeo E
FAU - Cognet, Celine
AU  - Cognet C
FAU - Martinetti, Miryam
AU  - Martinetti M
FAU - Maccario, Rita
AU  - Maccario R
FAU - Mingari, Maria Cristina
AU  - Mingari MC
FAU - Vivier, Eric
AU  - Vivier E
FAU - Moretta, Lorenzo
AU  - Moretta L
FAU - Locatelli, Franco
AU  - Locatelli F
FAU - Moretta, Alessandro
AU  - Moretta A
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081022
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (KIR2DS2 protein, human)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Adolescent
MH  - Cells, Cultured
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Graft vs Leukemia Effect/immunology
MH  - *Hematopoietic Stem Cell Transplantation/methods
MH  - Histocompatibility Testing
MH  - Humans
MH  - Killer Cells, Natural/immunology/*physiology
MH  - Leukemia/immunology/*therapy
MH  - Male
MH  - Patient Selection
MH  - Receptors, KIR/*metabolism/*physiology
MH  - Substrate Specificity
MH  - *Tissue Donors
MH  - Transplantation/physiology
MH  - Transplantation, Homologous
MH  - Young Adult
EDAT- 2008/10/24 09:00
MHDA- 2009/05/02 09:00
CRDT- 2008/10/24 09:00
PHST- 2008/10/24 09:00 [pubmed]
PHST- 2009/05/02 09:00 [medline]
PHST- 2008/10/24 09:00 [entrez]
AID - S0006-4971(20)39433-7 [pii]
AID - 10.1182/blood-2008-06-164103 [doi]
PST - ppublish
SO  - Blood. 2009 Mar 26;113(13):3119-29. doi: 10.1182/blood-2008-06-164103. Epub 2008 
      Oct 22.