NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations:: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect

被引:203
作者
Nguyen, S
Dhedin, N
Vernant, JP
Kuentz, M
Al Jijakli, A
Rouas-Freiss, N
Carosella, ED
Boudifa, A
Debré, P
Vieillard, V
机构
[1] Hop La Pitie Salpetriere, INSERM, U543, Lab Immunol Cellulaire & Tissulaire, F-75013 Paris, France
[2] Hop La Pitie Salpetriere, Serv Hematol Clin, F-75013 Paris, France
[3] Hop Henri Mondor, Serv Hematol Clin, F-94010 Creteil, France
[4] Hop St Louis, CEA, Paris, France
关键词
D O I
10.1182/blood-2004-10-4113
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Natural killer (NK) cell alloreactivity is reported to mediate strong GvL (graft versus leukemia) effect in patients after haploidentical stem-cell transplantation (SCT) for acute myeloid leukemia (AML). Because subsequent immune reconstitution remains a major concern, we studied NK-cell recovery in 10 patients with AML who received haplomismatched SC transplants, among whom no GvL effect was observed, despite the mismatched immunoglobulln-like receptor (KIR) ligand in the GvH direction for 8 of 10 patients. NK cells generated after SCT exhibited an immature phenotype: the cytotoxic CD3-CD56(dim) subset was small, expression of KIRs and NKp30 was reduced, while CD94/NKG2A expression was increased. This phenotype was associated to in vitro lower levels of cytotoxicity against a K562 cell line and against primary mismatched AML blasts than donor samples. This impaired lysis was correlated with CD94/NKG2A expression in NK cells. Blockading CD94/NKG2A restored lysis against the AML blasts, which all expressed HILA-E, the ligand for CD94/ NKG2A. Our present study allows a better understanding of the NK-cell differentiation after SCT. These results revealed that the NK cells generated after haplomismatched SCT are blocked at an immature state characterized by specific phenotypic features and impaired functioning, having potential impact for immune responsiveness and transplantation outcome. (c) 2005 by The American Society of Hematology.
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页码:4135 / 4142
页数:8
相关论文
共 45 条
[11]   CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2:: a potential new link between adaptive and innate immunity [J].
Fehniger, TA ;
Cooper, MA ;
Nuovo, GJ ;
Cella, M ;
Facchetti, F ;
Colonna, M ;
Caligiuri, MA .
BLOOD, 2003, 101 (08) :3052-3057
[12]   The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic [J].
Ferlazzo, G ;
Thomas, D ;
Lin, SL ;
Goodman, K ;
Morandi, B ;
Muller, WA ;
Moretta, A ;
Münz, C .
JOURNAL OF IMMUNOLOGY, 2004, 172 (03) :1455-1462
[13]   Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells [J].
Ferlazzo, G ;
Tsang, ML ;
Moretta, L ;
Melioli, G ;
Steinman, RM ;
Münz, C .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (03) :343-351
[14]  
Frey M, 1998, J IMMUNOL, V161, P400
[15]   Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors [J].
Giebel, S ;
Locatelli, F ;
Lamparelli, T ;
Velardi, A ;
Davies, S ;
Frumento, G ;
Maccario, R ;
Bonetti, F ;
Wojnar, J ;
Martinetti, M ;
Frassoni, F ;
Giorgiani, G ;
Bacigalupo, A ;
Holowiecki, J .
BLOOD, 2003, 102 (03) :814-819
[16]  
JACOBS R, 1992, BLOOD, V79, P3239
[17]   A prospective analysis of immune recovery in children following allogeneic transplantation of T-cell-depleted or non-T-cell-depleted hematopoietic cells from HLA-disparate family donors [J].
Kalwak, K ;
Moson, I ;
Cwian, J ;
Gorczynska, E ;
Toporski, J ;
Turkiewicz, D ;
Latos-Grazynska, E ;
Chybicka, A .
TRANSPLANTATION PROCEEDINGS, 2003, 35 (04) :1551-1555
[18]  
Lamb LS, 1998, BONE MARROW TRANSPL, V21, P461
[19]   NK cell receptors [J].
Lanier, LL .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :359-393
[20]  
Lee N, 1998, J IMMUNOL, V160, P4951