Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation

被引:779
作者
Ruggeri, L
Capanni, M
Casucci, M
Volpi, I
Tosti, A
Perruccio, K
Urbani, E
Negrin, RS
Martelli, MF
Velardi, A [1 ]
机构
[1] Univ Perugia, Monteluce Policlin, Sez Ematol & Immunol Clin, Div Hematol & Clin Immunol, I-06122 Perugia, Italy
[2] Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy
[3] Stanford Univ, Dept Med, Div Bone Marrow Transplantat, Stanford, CA 94305 USA
关键词
D O I
10.1182/blood.V94.1.333.413a31_333_339
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Because of the expression of inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I allotypes, a person's natural killer (NK) cells will not recognize and will, therefore, kill cells from individuals lacking his/her KIR epitopes. This study investigated the role of NK cell alloreactivity in human HLA haplotype-mismatched hematopoietic stem cell transplantation and, specifically, the role Of the three major NK specificities, ie, those for HLA-C group lr HLA-C group 2, and HLA-Bw4 alleles, In 20 of 60 donor-recipient pairs, KIR epitope incompatibility and functional analyses of donor NK cell clones predicted donor NK cells could cause graft-versus-host (GVH)/graft-versus-leukemia (GVL) reactions. NK cell clones of donor origin were obtained from transplanted recipients and tested for lysis of recipient's cryopreserved pretransplant lymphocytes. Despite the absence of GVH disease, we detected high frequencies of NK clones which killed recipient's target cells. Lysis followed the rules of NK cell alloreactivity, being blocked only by the MHC class I KIR epitope which was missing in the recipient. The alloreactive NK clones also killed the allogeneic leukemia. Transplants from these KIR epitope incompatible donors had higher engraftment rates. Therefore, a GVL effector and engraftment facilitating mechanism, which is independent of T-cell-mediated GVH reactions, may be operational in HLA mismatched hematopoietic cell transplants. (C) 1999 by The American Society of Hematology.
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页码:333 / 339
页数:7
相关论文
共 34 条
  • [21] NK cell receptors
    Lanier, LL
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 : 359 - 393
  • [22] LAVER J, 1987, BLOOD, V70, P1966
  • [23] HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A
    Lee, N
    Llano, M
    Carretero, M
    Ishitani, A
    Navarro, F
    Lopez-Botet, M
    Geraghty, DE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) : 5199 - 5204
  • [24] HLA class I specific inhibitory receptors
    Moretta, A
    Moretta, L
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1997, 9 (05) : 694 - 701
  • [25] The natural killer cell receptor specific for HLA-A allotypes: A novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer
    Pende, D
    Biassoni, R
    Cantoni, C
    Verdiani, S
    Falco, M
    DiDonato, C
    Accame, L
    Bottino, C
    Moretta, A
    Moretta, L
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) : 505 - 518
  • [26] Salcedo M, 1998, EUR J IMMUNOL, V28, P1315, DOI 10.1002/(SICI)1521-4141(199804)28:04<1315::AID-IMMU1315>3.0.CO
  • [27] 2-2
  • [28] HEMATOPOIETIC-CELLS AND RADIORESISTANT HOST ELEMENTS INFLUENCE NATURAL-KILLER-CELL DIFFERENTIATION
    SYKES, M
    HARTY, MW
    KARLHOFER, FM
    PEARSON, DA
    SZOT, G
    YOKOYAMA, W
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (01) : 223 - 229
  • [29] UHAREK L, 1993, BONE MARROW TRANSPL, V12, P57
  • [30] Human diversity in killer cell inhibitory receptor genes
    Uhrberg, M
    Valiante, NM
    Shum, BP
    Shilling, HG
    Lienert-Weidenbach, K
    Corliss, B
    Tyan, D
    Lanier, LL
    Parham, P
    [J]. IMMUNITY, 1997, 7 (06) : 753 - 763