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http://purl.uniprot.org/citations/21554925http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21554925http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To investigate the presence of T cells with natural killer cell receptors (NKR) in paroxysmal nocturnal hemoglobinuria (PNH), and their potential involvement in clonal expansion of glycosylphosphatidylinositol (GPI)-deficient hematopoietic stem cells by selective immune attack to normal and not GPI-deficient hematopoietic stem cells.

Materials and methods

By flow cytometry, the frequency and number of T cells expressing NKR was evaluated in 39 PNH patients and compared to healthy controls. Elevated T cell subsets in PNH were assessed for differential cytotoxic lysis of GPI(+) and GPI(-) CD34(+) hematopoietic progenitor cell lines.

Results

In PNH patients, the frequency (p < 0.001) and absolute number of T cells expressing the NKR CD56 (p = 0.01) were significantly increased. Furthermore, a higher percentage of T cells expressed the activating NKR NKG2D (p < 0.01), NKG2C (p < 0.01), and KIR2DS4 (p = 0.01). Further characterization showed that these populations predominantly consist of CD8(+) effector memory CD45RA(+) T cells (T(EMRA)). NKR(+) cytotoxic T-lymphocyte lines isolated from PNH patient peripheral blood and bone marrow displayed high cytotoxicity towards CD34(+) hematopoietic progenitor cell lines and K562 cells, suggesting major histocompatibility complex class I-independent cytotoxicity. These cytotoxic T lymphocyte (CTL) lines are capable of differential lysis of GPI(+) and GPI(-) hematopoietic cell lines, however, not in all cases. This suggests that multiple factors, such as the highly activated status of in vitro cultured CTLs, influence whether GPI-dependent lysis occurs.

Conclusions

The increased frequency of CD8(+) effector-memory T cells with activating NKR and cytotoxicity toward hematopoietic cell lines suggests involvement in bone marrow failure and clonal expansion in PNH."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.org/dc/terms/identifier"doi:10.1016/j.exphem.2011.04.003"xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"de Witte T."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"Preijers F."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"van der Meer A."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"Dolstra H."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"Muus P."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"Withaar M."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/author"van Bijnen S.T."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/name"Exp Hematol"xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/pages"751-62.e1-3"xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/title"T cells expressing the activating NK-cell receptors KIR2DS4, NKG2C and NKG2D are elevated in paroxysmal nocturnal hemoglobinuria and cytotoxic toward hematopoietic progenitor cell lines."xsd:string
http://purl.uniprot.org/citations/21554925http://purl.uniprot.org/core/volume"39"xsd:string
http://purl.uniprot.org/citations/21554925http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21554925
http://purl.uniprot.org/citations/21554925http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21554925
http://purl.uniprot.org/uniprot/#_A0A0C4ZN05-mappedCitation-21554925http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21554925
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http://purl.uniprot.org/uniprot/#_A0A0C4ZN30-mappedCitation-21554925http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21554925
http://purl.uniprot.org/uniprot/#_A0A0C4ZQX6-mappedCitation-21554925http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21554925
http://purl.uniprot.org/uniprot/#_A0A1W2PR63-mappedCitation-21554925http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21554925
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http://purl.uniprot.org/uniprot/#_A0A376A919-mappedCitation-21554925http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21554925
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