Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes

Renato Zambello, Michela Falco, Mariella Della Chiesa, Livio Trentin, Davide Carollo, Roberta Castriconi, Giovanna Cannas, Simona Carlomagno, Anna Cabrelle, Thierry Lamy, Carlo Agostini, Alessandro Moretta, Gianpietro Semenzato, Massimo Vitale

Research output: Contribution to journalArticle

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Abstract

Using monoclonal antibodies (mAbs) specific for different natural killer (NK) receptors, we studied the lymphocyte population from 18 patients with NK-type lymphoproliferative disease of granular lymphocytes (LDGL). The analysis of both resting and cultured NK cell populations demonstrated that these patients are frequently characterized by NK cells displaying a homogeneous staining with given anti-killer Ig-like receptor (anti-KIR) mAb (11 of 18 patients). In most patients NK cells were characterized by the CD94/NKG2A+ phenotype, whereas only a minor fraction of the cases expressed CD94/NKG2C. In 7 of these patients we could also assess the function of the various NK receptors. Remarkably those KIR molecules that, in each patient, homogeneously marked the NK cell expansion were found to display an activating function as determined by cross-linking with specific anti-KIR mAb. The KIR genotype analysis performed in 13 of 18 cases revealed that in NK-type LDGL certain activating KIRs, as well as certain infrequent KIR genotypes, were detected with higher frequencies as compared to previously analyzed healthy donors. Moreover, most KIR genotypes included multiple genes coding for activating KIRs. The analysis of non-HLA-specific triggering receptors indicated that the natural cytotoxicity receptors (NKp46, NKp30) were expressed at significantly low levels in freshly drawn NK cells from most patients analyzed. However, in most instances the expression of NKp46 and NKp30 could be up-regulated on culture in interleukin 2. Our data indicate that in NK-LDGL the expanded subset is frequently characterized by the expression of a given activating KIR, suggesting a direct role for these molecules in the pathogenetic mechanisms of this disorder.

Original languageEnglish
Pages (from-to)1797-1805
Number of pages9
JournalBlood
Volume102
Issue number5
DOIs
Publication statusPublished - Sep 1 2003

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Large Granular Lymphocytic Leukemia
Lymphocytes
Cytotoxicity
Natural Killer Cells
Natural Cytotoxicity Triggering Receptor 1
Genotype
Natural Cytotoxicity Triggering Receptors
Molecules
Natural Cytotoxicity Triggering Receptor 3
Interleukin-2
Genes
Monoclonal Antibodies
Cells
Lymphocyte Subsets
Population
Cultured Cells
Tissue Donors
Staining and Labeling
Phenotype

ASJC Scopus subject areas

  • Hematology

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Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes. / Zambello, Renato; Falco, Michela; Della Chiesa, Mariella; Trentin, Livio; Carollo, Davide; Castriconi, Roberta; Cannas, Giovanna; Carlomagno, Simona; Cabrelle, Anna; Lamy, Thierry; Agostini, Carlo; Moretta, Alessandro; Semenzato, Gianpietro; Vitale, Massimo.

In: Blood, Vol. 102, No. 5, 01.09.2003, p. 1797-1805.

Research output: Contribution to journalArticle

Zambello, R, Falco, M, Della Chiesa, M, Trentin, L, Carollo, D, Castriconi, R, Cannas, G, Carlomagno, S, Cabrelle, A, Lamy, T, Agostini, C, Moretta, A, Semenzato, G & Vitale, M 2003, 'Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes', Blood, vol. 102, no. 5, pp. 1797-1805. https://doi.org/10.1182/blood-2002-12-3898
Zambello, Renato ; Falco, Michela ; Della Chiesa, Mariella ; Trentin, Livio ; Carollo, Davide ; Castriconi, Roberta ; Cannas, Giovanna ; Carlomagno, Simona ; Cabrelle, Anna ; Lamy, Thierry ; Agostini, Carlo ; Moretta, Alessandro ; Semenzato, Gianpietro ; Vitale, Massimo. / Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes. In: Blood. 2003 ; Vol. 102, No. 5. pp. 1797-1805.
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AU - Carollo, Davide

AU - Castriconi, Roberta

AU - Cannas, Giovanna

AU - Carlomagno, Simona

AU - Cabrelle, Anna

AU - Lamy, Thierry

AU - Agostini, Carlo

AU - Moretta, Alessandro

AU - Semenzato, Gianpietro

AU - Vitale, Massimo

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N2 - Using monoclonal antibodies (mAbs) specific for different natural killer (NK) receptors, we studied the lymphocyte population from 18 patients with NK-type lymphoproliferative disease of granular lymphocytes (LDGL). The analysis of both resting and cultured NK cell populations demonstrated that these patients are frequently characterized by NK cells displaying a homogeneous staining with given anti-killer Ig-like receptor (anti-KIR) mAb (11 of 18 patients). In most patients NK cells were characterized by the CD94/NKG2A+ phenotype, whereas only a minor fraction of the cases expressed CD94/NKG2C. In 7 of these patients we could also assess the function of the various NK receptors. Remarkably those KIR molecules that, in each patient, homogeneously marked the NK cell expansion were found to display an activating function as determined by cross-linking with specific anti-KIR mAb. The KIR genotype analysis performed in 13 of 18 cases revealed that in NK-type LDGL certain activating KIRs, as well as certain infrequent KIR genotypes, were detected with higher frequencies as compared to previously analyzed healthy donors. Moreover, most KIR genotypes included multiple genes coding for activating KIRs. The analysis of non-HLA-specific triggering receptors indicated that the natural cytotoxicity receptors (NKp46, NKp30) were expressed at significantly low levels in freshly drawn NK cells from most patients analyzed. However, in most instances the expression of NKp46 and NKp30 could be up-regulated on culture in interleukin 2. Our data indicate that in NK-LDGL the expanded subset is frequently characterized by the expression of a given activating KIR, suggesting a direct role for these molecules in the pathogenetic mechanisms of this disorder.

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