|
|
Blood, 15 December 2005, Vol. 106, No. 13, pp. 4370-4376.
Prepublished online as a Blood First Edition Paper on August 30, 2005; DOI 10.1182/blood-2005-04-1644.
Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation
Sarah Cooley,
Valarie McCullar,
Rosanna Wangen,
Tracy L. Bergemann,
Stephen Spellman,
Daniel J. Weisdorf, and
Jeffrey S. Miller
From the Division of Medical Hematology-Oncology and Transplantation, University of Minnesota Cancer Center, University of Minnesota, National Marrow Donor Program (NMDP), Minneapolis, MN.
Although unrelated hematopoietic cell transplantation (HCT) is curative for many hematologic malignancies, complications and relapse remain challenging obstacles. Natural killer (NK) cells, which recover quickly after transplantation, produce cytokines and express killer immunoglobulin-like receptors (KIRs) that regulate their cytotoxicity. Some clinical trials based on a KIR ligand mismatch strategy are associated with less relapse and increased survival, but results are mixed. We hypothesized that T cells in the graft may affect NK cell function and KIR expression after unrelated transplantation and that these differences correlate with clinical outcomes. NK cell function was evaluated using 77 paired samples from the National Marrow Donor Program Research Repository. Recipient NK cells at 100 days after both unmanipulated bone marrow (UBM) and T-cell depleted (TCD) transplants were compared with NK cells from their healthy donors. NK cells expressed fewer KIRs and produced more interferon (IFN- ) after UBM compared to TCD transplants. Multivariate models showed that increased NK cell IFN- production correlated with more acute graft-versus-host disease (GVHD), and decreased KIR expression correlated with inferior survival. These results support the notion that T cells in the graft affect NK cell reconstitution in vivo. Understanding these mechanisms may result in strategies to improve clinical outcomes from unrelated HCT.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
J. S. Miller
How killers kill
Blood,
July 15, 2008;
112(2):
213 - 213.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Vitale, F. Cottalasso, E. Montaldo, L. Moretta, and M. C. Mingari
Methylprednisolone induces preferential and rapid differentiation of CD34+ cord blood precursors toward NK cells
Int. Immunol.,
April 1, 2008;
20(4):
565 - 575.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Yu, G. Heller, J. Chewning, S. Kim, W. M. Yokoyama, and K. C. Hsu
Hierarchy of the Human Natural Killer Cell Response Is Determined by Class and Quantity of Inhibitory Receptors for Self-HLA-B and HLA-C Ligands
J. Immunol.,
November 1, 2007;
179(9):
5977 - 5989.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Wang, B. Grzywacz, D. Sukovich, V. McCullar, Q. Cao, A. B. Lee, B. R. Blazar, D. N. Cornfield, J. S. Miller, and M. R. Verneris
The unexpected effect of cyclosporin A on CD56+CD16 and CD56+CD16+ natural killer cell subpopulations
Blood,
September 1, 2007;
110(5):
1530 - 1539.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A. Cahill, D. Wenkert, S. A. Perlman, A. Steele, S. P. Coburn, W. H. McAlister, S. Mumm, and M. P. Whyte
Infantile Hypophosphatasia: Transplantation Therapy Trial Using Bone Fragments and Cultured Osteoblasts
J. Clin. Endocrinol. Metab.,
August 1, 2007;
92(8):
2923 - 2930.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Cooley, F. Xiao, M. Pitt, M. Gleason, V. McCullar, T. L. Bergemann, K. L. McQueen, L. A. Guethlein, P. Parham, and J. S. Miller
A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature
Blood,
July 15, 2007;
110(2):
578 - 586.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Ruggeri, A. Mancusi, M. Capanni, E. Urbani, A. Carotti, T. Aloisi, M. Stern, D. Pende, K. Perruccio, E. Burchielli, et al.
Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value.
Blood,
July 1, 2007;
110(1):
433 - 440.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Miller, S. Cooley, P. Parham, S. S. Farag, M. R. Verneris, K. L. McQueen, L. A. Guethlein, E. A. Trachtenberg, M. Haagenson, M. M. Horowitz, et al.
Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT
Blood,
June 1, 2007;
109(11):
5058 - 5061.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Grzywacz, N. Kataria, M. Sikora, R. A. Oostendorp, E. A. Dzierzak, B. R. Blazar, J. S. Miller, and M. R. Verneris
Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells
Blood,
December 1, 2006;
108(12):
3824 - 3833.
[Abstract]
[Full Text]
[PDF]
|
 |
|
| |