Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children
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Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children. / Pfeiffer, Matthias M; Feuchtinger, Tobias; Teltschik, Heiko-Manuel; Schumm, Michael; Müller, Ingo; Handgretinger, Rupert; Lang, Peter.
in: HAEMATOLOGICA, Jahrgang 95, Nr. 8, 01.08.2010, S. 1381-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Transfer › Begutachtung
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T1 - Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children
AU - Pfeiffer, Matthias M
AU - Feuchtinger, Tobias
AU - Teltschik, Heiko-Manuel
AU - Schumm, Michael
AU - Müller, Ingo
AU - Handgretinger, Rupert
AU - Lang, Peter
PY - 2010/8/1
Y1 - 2010/8/1
N2 - BACKGROUND: Natural killer cells have been demonstrated to exert remarkable graft-versus-leukemia effects after haploidentical transplantation. Acquisition of both, inhibiting and activating, receptors on developing natural killer cells is an important step in their functional maturation. Here, we report on the reconstitution of natural killer receptors after haploidentical transplantation of T-and B-cell (CD3/CD19) depleted grafts with co-transfusion of natural killer cells in children and its influence on natural killer cell activity and clinical outcome.DESIGN AND METHODS: We analyzed reconstitution patterns of natural killer receptors at different time intervals after haploidentical transplantation by multi-color flow cytometry. Natural killer cell activity and antibody-dependent cellular cytotoxicity was tested against cell lines and leukemic blasts in vitro. Survival was analyzed using Kaplan-Meier estimates.RESULTS: Recovery of CD56(+)/CD16(+) cells was fast with high cytolytic activity against K562 and strong antibody-dependent cellular cytotoxicity activity against neuroblastoma and leukemic blasts as early as day 14 posttransplant. KIR reconstitution showed a predominance of KIR negative natural killer cells early after transplantation and an early reconstitution of CD158b compared to CD158a and CD158e. These differences were independent of presence or absence of the corresponding KIR ligands in donors or recipients. This reconstitution pattern was associated with a higher relapse probability of patients homozygous for HLA-C1-alleles compared to patients homozygous or even heterozygous for HLA-C2-alleles.CONCLUSIONS: Our results indicate a fast recovery of functional and alloreactive natural killer cells with a constant KIR pattern after haploidentical transplantation with T- and B-cell depleted grafts. Moreover, these natural killer cells can mediate antibody-dependent cellular cytotoxicity and therefore may allow for an early use of antibodies against residual malignant cells.
AB - BACKGROUND: Natural killer cells have been demonstrated to exert remarkable graft-versus-leukemia effects after haploidentical transplantation. Acquisition of both, inhibiting and activating, receptors on developing natural killer cells is an important step in their functional maturation. Here, we report on the reconstitution of natural killer receptors after haploidentical transplantation of T-and B-cell (CD3/CD19) depleted grafts with co-transfusion of natural killer cells in children and its influence on natural killer cell activity and clinical outcome.DESIGN AND METHODS: We analyzed reconstitution patterns of natural killer receptors at different time intervals after haploidentical transplantation by multi-color flow cytometry. Natural killer cell activity and antibody-dependent cellular cytotoxicity was tested against cell lines and leukemic blasts in vitro. Survival was analyzed using Kaplan-Meier estimates.RESULTS: Recovery of CD56(+)/CD16(+) cells was fast with high cytolytic activity against K562 and strong antibody-dependent cellular cytotoxicity activity against neuroblastoma and leukemic blasts as early as day 14 posttransplant. KIR reconstitution showed a predominance of KIR negative natural killer cells early after transplantation and an early reconstitution of CD158b compared to CD158a and CD158e. These differences were independent of presence or absence of the corresponding KIR ligands in donors or recipients. This reconstitution pattern was associated with a higher relapse probability of patients homozygous for HLA-C1-alleles compared to patients homozygous or even heterozygous for HLA-C2-alleles.CONCLUSIONS: Our results indicate a fast recovery of functional and alloreactive natural killer cells with a constant KIR pattern after haploidentical transplantation with T- and B-cell depleted grafts. Moreover, these natural killer cells can mediate antibody-dependent cellular cytotoxicity and therefore may allow for an early use of antibodies against residual malignant cells.
KW - Adolescent
KW - Adult
KW - Alleles
KW - Antigens, CD3
KW - Antigens, CD56
KW - B-Lymphocytes
KW - Child
KW - Child, Preschool
KW - Cytotoxicity, Immunologic
KW - Flow Cytometry
KW - HLA-C Antigens
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Infant
KW - K562 Cells
KW - Killer Cells, Natural
KW - Receptors, IgG
KW - Receptors, Natural Killer Cell
KW - Recurrence
KW - T-Lymphocytes
KW - Young Adult
U2 - 10.3324/haematol.2009.021121
DO - 10.3324/haematol.2009.021121
M3 - SCORING: Journal article
C2 - 20145268
VL - 95
SP - 1381
EP - 1388
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 8
ER -