Phenotypic and functional analysis of the HLA-class I-specific inhibitory receptors of natural killer cells isolated from peripheral blood of patients undergoing bone marrow transplantation from matched unrelated donors

Chiara Vitale, Anna Pitto, Federica Benvenuto, Marco Ponte, Rosa Bellomo, Francesco Frassoni, Maria Cristina Mingari, Andrea Bacigalupo, Lorenzo Moretta

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20 Citations (Scopus)

Abstract

Introduction: Limited information is available on the natural killer cell reconstitution after bone marrow transplantation and on the possible role of these cells in graft-versus-host-disease. Materials and methods: Blood samples were collected at different time intervals after transplantation. Lymphocytes were analyzed for informative markers by immunocytofluorimetric analysis. Natural killer cells derived from patients undergoing matched unrelated donor transplant were cloned by limiting dilution in the presence of phytohemoagglutinin and IL2. The natural killer cell clones were analyzed for cytolytic activity. Results: In the nine patients analyzed undergoing transplantation from sibling donors, the majority of peripheral blood lymphocytes during the first 80 d after BMT were represented by T lymphocytes, while in the 15 patients undergoing matched unrelated donor transplant natural killer cells consistently outnumbered T lymphocytes. During the early phases after transplantation, most CD56+CD3- natural killer cells did not express CD16 which was expressed at later intervals. Analysis of the inhibitory receptors specific for HLA-class I molecules showed that CD94/NKG2A, specific for HLA-E, unlike normal donors, was expressed by all natural killer cells including the early appearing CD16-negative ones. Killer inhibitory receptors of the Ig superfamily were expressed late and in low percentages after transplantation and were always coexpressed with CD94/NKG2A. Natural killer-cell clones efficiently lysed the HLA-class I-negative cell lines K562 and 721-221. Natural killer-cell populations or clones isolated from patients with graft-versus-host-disease, failed to lyse donor or recipient derived phytohemoagglutinin-induced lymphoblasts. Conclusion: Our analysis shows that (1) recipients of matched unrelated donors transplants exhibit a high proportion of NK cells (2) all NK cells express CD94/NKG2A while the HLA-class I-specific inhibitory receptors of Ig superfamily appear at later stages and (3) donor NK cells do not lysed donor or recipient target cells.

Original languageEnglish
Pages (from-to)136-144
Number of pages9
JournalHematology Journal
Volume1
Issue number2
Publication statusPublished - 2000

Fingerprint

Natural Killer Cell Receptors
Unrelated Donors
Bone Marrow Transplantation
Natural Killer Cells
Tissue Donors
Transplantation
Clone Cells
Graft vs Host Disease
Transplants
KIR Receptors
Lymphocytes
T-Lymphocytes
Interleukin-2
Siblings

Keywords

  • Bone marrow transplantation
  • Killer inhibitory receptors
  • Lymphocyte development
  • Natural killer cells

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Phenotypic and functional analysis of the HLA-class I-specific inhibitory receptors of natural killer cells isolated from peripheral blood of patients undergoing bone marrow transplantation from matched unrelated donors",
abstract = "Introduction: Limited information is available on the natural killer cell reconstitution after bone marrow transplantation and on the possible role of these cells in graft-versus-host-disease. Materials and methods: Blood samples were collected at different time intervals after transplantation. Lymphocytes were analyzed for informative markers by immunocytofluorimetric analysis. Natural killer cells derived from patients undergoing matched unrelated donor transplant were cloned by limiting dilution in the presence of phytohemoagglutinin and IL2. The natural killer cell clones were analyzed for cytolytic activity. Results: In the nine patients analyzed undergoing transplantation from sibling donors, the majority of peripheral blood lymphocytes during the first 80 d after BMT were represented by T lymphocytes, while in the 15 patients undergoing matched unrelated donor transplant natural killer cells consistently outnumbered T lymphocytes. During the early phases after transplantation, most CD56+CD3- natural killer cells did not express CD16 which was expressed at later intervals. Analysis of the inhibitory receptors specific for HLA-class I molecules showed that CD94/NKG2A, specific for HLA-E, unlike normal donors, was expressed by all natural killer cells including the early appearing CD16-negative ones. Killer inhibitory receptors of the Ig superfamily were expressed late and in low percentages after transplantation and were always coexpressed with CD94/NKG2A. Natural killer-cell clones efficiently lysed the HLA-class I-negative cell lines K562 and 721-221. Natural killer-cell populations or clones isolated from patients with graft-versus-host-disease, failed to lyse donor or recipient derived phytohemoagglutinin-induced lymphoblasts. Conclusion: Our analysis shows that (1) recipients of matched unrelated donors transplants exhibit a high proportion of NK cells (2) all NK cells express CD94/NKG2A while the HLA-class I-specific inhibitory receptors of Ig superfamily appear at later stages and (3) donor NK cells do not lysed donor or recipient target cells.",
keywords = "Bone marrow transplantation, Killer inhibitory receptors, Lymphocyte development, Natural killer cells",
author = "Chiara Vitale and Anna Pitto and Federica Benvenuto and Marco Ponte and Rosa Bellomo and Francesco Frassoni and Mingari, {Maria Cristina} and Andrea Bacigalupo and Lorenzo Moretta",
year = "2000",
language = "English",
volume = "1",
pages = "136--144",
journal = "Hematology Journal",
issn = "1466-4860",
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number = "2",

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TY - JOUR

T1 - Phenotypic and functional analysis of the HLA-class I-specific inhibitory receptors of natural killer cells isolated from peripheral blood of patients undergoing bone marrow transplantation from matched unrelated donors

AU - Vitale, Chiara

AU - Pitto, Anna

AU - Benvenuto, Federica

AU - Ponte, Marco

AU - Bellomo, Rosa

AU - Frassoni, Francesco

AU - Mingari, Maria Cristina

AU - Bacigalupo, Andrea

AU - Moretta, Lorenzo

PY - 2000

Y1 - 2000

N2 - Introduction: Limited information is available on the natural killer cell reconstitution after bone marrow transplantation and on the possible role of these cells in graft-versus-host-disease. Materials and methods: Blood samples were collected at different time intervals after transplantation. Lymphocytes were analyzed for informative markers by immunocytofluorimetric analysis. Natural killer cells derived from patients undergoing matched unrelated donor transplant were cloned by limiting dilution in the presence of phytohemoagglutinin and IL2. The natural killer cell clones were analyzed for cytolytic activity. Results: In the nine patients analyzed undergoing transplantation from sibling donors, the majority of peripheral blood lymphocytes during the first 80 d after BMT were represented by T lymphocytes, while in the 15 patients undergoing matched unrelated donor transplant natural killer cells consistently outnumbered T lymphocytes. During the early phases after transplantation, most CD56+CD3- natural killer cells did not express CD16 which was expressed at later intervals. Analysis of the inhibitory receptors specific for HLA-class I molecules showed that CD94/NKG2A, specific for HLA-E, unlike normal donors, was expressed by all natural killer cells including the early appearing CD16-negative ones. Killer inhibitory receptors of the Ig superfamily were expressed late and in low percentages after transplantation and were always coexpressed with CD94/NKG2A. Natural killer-cell clones efficiently lysed the HLA-class I-negative cell lines K562 and 721-221. Natural killer-cell populations or clones isolated from patients with graft-versus-host-disease, failed to lyse donor or recipient derived phytohemoagglutinin-induced lymphoblasts. Conclusion: Our analysis shows that (1) recipients of matched unrelated donors transplants exhibit a high proportion of NK cells (2) all NK cells express CD94/NKG2A while the HLA-class I-specific inhibitory receptors of Ig superfamily appear at later stages and (3) donor NK cells do not lysed donor or recipient target cells.

AB - Introduction: Limited information is available on the natural killer cell reconstitution after bone marrow transplantation and on the possible role of these cells in graft-versus-host-disease. Materials and methods: Blood samples were collected at different time intervals after transplantation. Lymphocytes were analyzed for informative markers by immunocytofluorimetric analysis. Natural killer cells derived from patients undergoing matched unrelated donor transplant were cloned by limiting dilution in the presence of phytohemoagglutinin and IL2. The natural killer cell clones were analyzed for cytolytic activity. Results: In the nine patients analyzed undergoing transplantation from sibling donors, the majority of peripheral blood lymphocytes during the first 80 d after BMT were represented by T lymphocytes, while in the 15 patients undergoing matched unrelated donor transplant natural killer cells consistently outnumbered T lymphocytes. During the early phases after transplantation, most CD56+CD3- natural killer cells did not express CD16 which was expressed at later intervals. Analysis of the inhibitory receptors specific for HLA-class I molecules showed that CD94/NKG2A, specific for HLA-E, unlike normal donors, was expressed by all natural killer cells including the early appearing CD16-negative ones. Killer inhibitory receptors of the Ig superfamily were expressed late and in low percentages after transplantation and were always coexpressed with CD94/NKG2A. Natural killer-cell clones efficiently lysed the HLA-class I-negative cell lines K562 and 721-221. Natural killer-cell populations or clones isolated from patients with graft-versus-host-disease, failed to lyse donor or recipient derived phytohemoagglutinin-induced lymphoblasts. Conclusion: Our analysis shows that (1) recipients of matched unrelated donors transplants exhibit a high proportion of NK cells (2) all NK cells express CD94/NKG2A while the HLA-class I-specific inhibitory receptors of Ig superfamily appear at later stages and (3) donor NK cells do not lysed donor or recipient target cells.

KW - Bone marrow transplantation

KW - Killer inhibitory receptors

KW - Lymphocyte development

KW - Natural killer cells

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