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Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants
Loredana Ruggeri,1Marusca Capanni,1Elena Urbani,1Katia Perruccio,1Warren D. Shlomchik,2Antonella Tosti,1Sabrina Posati,1Daniela Rogaia,1Francesco Frassoni,3Franco Aversa,1Massimo F. Martelli,1Andrea Velardi1*
T cells that accompany allogeneic hematopoietic grafts for treating
leukemia enhance engraftment and mediate the graft-versus-leukemiaeffect. Unfortunately, alloreactive T cells also cause
graft-versus-hostdisease (GVHD). T cell depletion prevents GVHD but
increases therisk of graft rejection and leukemic relapse. In human
transplants,we show that donor-versus-recipient natural killer
(NK)-cell alloreactivitycould eliminate leukemia relapse and
graft rejection and protectpatients against GVHD. In mice, the
pretransplant infusion ofalloreactive NK cells obviated the need for
high-intensity conditioningand reduced GVHD. NK cell alloreactivity
may thus provide a powerfultool for enhancing the efficacy and safety
of allogeneic hematopoietictransplantation.
1 Department of Clinical and Experimental
Medicine, Section of Hematology and Clinical Immunology, Perugia
University School of Medicine, Perugia, Italy.
2 Department of Medicine, Sections of Hematology and
Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.
3 Department of Hematology, Ospedale San Martino,
Genoa, Italy.
*
To whom correspondence should be addressed. E-mail:
velardi{at}unipg.it
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I. B. Villalobos, Y. Takahashi, Y. Akatsuka, H. Muramatsu, N. Nishio, A. Hama, H. Yagasaki, H. Saji, M. Kato, S. Ogawa, et al. (2010)
Blood
115, 3158-3161
|Abstract »|Full Text »|PDF »
CD137 ligand mediates opposite effects in human and mouse NK cells and impairs NK-cell reactivity against human acute myeloid leukemia cells.
T. Baessler, J. E. Charton, B. J. Schmiedel, F. Grunebach, M. Krusch, A. Wacker, H. G. Rammensee, and H. R. Salih (2010)
Blood
115, 3058-3069
|Abstract »|Full Text »|PDF »
NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation.
A. T. Bjorklund, M. Schaffer, C. Fauriat, O. Ringden, M. Remberger, C. Hammarstedt, A. J. Barrett, P. Ljungman, H.-G. Ljunggren, and K.-J. Malmberg (2010)
Blood
115, 2686-2694
|Abstract »|Full Text »|PDF »
In Vivo Role of Flt3 Ligand and Dendritic Cells in NK Cell Homeostasis.
M. Guimond, A. G. Freud, H. C. Mao, J. Yu, B. W. Blaser, J. W. Leong, J. B. Vandeusen, A. Dorrance, J. Zhang, C. L. Mackall, et al. (2010)
J. Immunol.
184, 2769-2775
|Abstract »|Full Text »|PDF »
My approach to the immunogenetics of haematopoietic stem cell transplant matching.
Natural Killer Cell Consolidation for Acute Myelogenous Leukemia: A Cell Therapy Ready for Prime Time?.
M. R. Verneris and S. A. Grupp (2010)
J. Clin. Oncol.
28, 909-910
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Stem cell transplantation for autoimmune diseases.
T. Hugle and T. Daikeler (2010)
Haematologica
95, 185-188
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A Small, Variable, and Irregular Killer Cell Ig-Like Receptor Locus Accompanies the Absence of MHC-C and MHC-G in Gibbons.
L. Abi-Rached, H. Kuhl, C. Roos, B. ten Hallers, B. Zhu, L. Carbone, P. J. de Jong, A. R. Mootnick, F. Knaust, R. Reinhardt, et al. (2010)
J. Immunol.
184, 1379-1391
|Abstract »|Full Text »|PDF »
In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus.
B. Meek, S. Cloosen, C. Borsotti, C. H. M. J. Van Elssen, J. Vanderlocht, M. C. A. Schnijderberg, M. W. M. van der Poel, B. Leewis, R. Hesselink, M. G. Manz, et al. (2010)
Blood
115, 261-264
|Abstract »|Full Text »|PDF »
MICA-129 genotype, soluble MICA, and anti-MICA antibodies as biomarkers of chronic graft-versus-host disease.
W. Boukouaci, M. Busson, R. Peffault de Latour, V. Rocha, C. Suberbielle, D. Bengoufa, N. Dulphy, P. Haas, C. Scieux, H. Amroun, et al. (2009)
Blood
114, 5216-5224
|Abstract »|Full Text »|PDF »
The Human Ortholog of Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Fusion Protein Induces Potent Ex vivo Natural Killer Cell Activation and Maturation.
C. Penafuerte, N. Bautista-Lopez, B. Mohamed-Rachid, J.-P. Routy, and J. Galipeau (2009)
Cancer Res.
69, 9020-9028
|Abstract »|Full Text »|PDF »
Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction.
E. Marcenaro, C. Cantoni, S. Pesce, C. Prato, D. Pende, S. Agaugue, L. Moretta, and A. Moretta (2009)
Blood
114, 4108-4116
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Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands.
K. Gendzekhadze, P. J. Norman, L. Abi-Rached, T. Graef, A. K. Moesta, Z. Layrisse, and P. Parham (2009)
PNAS
106, 18692-18697
|Abstract »|Full Text »|PDF »
Loss of matrix metalloproteinase 2 in platelets reduces arterial thrombosis in vivo.
S. Momi, E. Falcinelli, S. Giannini, L. Ruggeri, L. Cecchetti, T. Corazzi, C. Libert, and P. Gresele (2009)
J. Exp. Med.
206, 2365-2379
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