Functional inhibitory human leucocyte antigen class I receptors on natural killer (NK) cells in patients with chronic NK lymphocytosis

Warren, Hilary S.; Christiansen, Frank; Witt, Campbell S.

doi:10.1046/j.1365-2141.2003.04342.x

Cited by 14 publications

(10 citation statements)

References 48 publications

(66 reference statements)

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“…Previous studies have also demonstrated that NK cells of LDGL patients express restricted NKRs (analysed by a panel of NKR monoclonal antibodies), and their results suggest that this correlates with monoclonal or oligoclonal NK cell expansion (Hoffmann et al , 2000; Mori et al , 2001; Morice et al , 2003; Warren et al , 2003). In the present study, CD94 expression was observed in all NK‐LDGL patients, whereas CD161 and KIR expression was observed in limited numbers of patients.…”

Section: Discussionmentioning

confidence: 89%

Characteristic expansion of CD45RA⁺ CD27⁻ CD28⁻ CCR7⁻ lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

Mitsui¹,

Maekawa

Yamane³

et al. 2004

Br J Haematol

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Summary We analysed the cell surface expression of chemokine receptors and natural killer receptors (NKRs) in addition to conventional T‐ and natural killer (NK)‐cell markers in patients with lymphoproliferative disease of granular lymphocytes (LDGL), and compared results between NK‐ and T‐LDGL subgroups. The subjects of this study were 15 LDGL patients: four NK‐LDGL and 11 T‐LDGL [six CD8+ T‐cell receptor (TCR) αβ+, four CD4+ TCRαβ+ and one CD8+ TCRγδ+] cases. Flow cytometric analysis showed that the expanding cells had a common phenotype, CD45RA+ CD27− CD28− CCR7−, in NK‐ and T‐LDGL patients irrespective of differences in TCR status. There were no marked differences in the expression patterns of chemokine receptors between NK‐ and T‐LDGL patients. Although restricted NKR subsets were expressed on both NK‐ and T‐large granular lymphocytes (LGLs), CD94 was the most widely expressed marker. These findings may be unique to cells of LDGL cases, because normal CD56dim NK cells frequently express killer cell immunoglobulin‐like receptors. Furthermore, analysis of NKR expression was repeated over an interval of more than 6 months, and fluctuations of NKR repertoire in the LGL clones were minimal.

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Section: Discussionmentioning

confidence: 89%

Characteristic expansion of CD45RA⁺ CD27⁻ CD28⁻ CCR7⁻ lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

Mitsui¹,

Maekawa

Yamane³

et al. 2004

Br J Haematol

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“…Nevertheless, autoimmune manifestations are not frequent in these patients. Several studies suggest that the fail-safe mechanism in LDGL patients could be represented by the expression of inhibitory receptors such as CD94/NKG2A [34,35].…”

Section: Introductionmentioning

confidence: 99%

NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease

Angelini

Zambello

Galandrini

et al. 2010

Journal of Leukocyte Biology

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The CD94/NKG2 complex is expressed on T and NK lymphocytes. CD94 molecules covalently associate to activating or inhibitory NKG2 molecules, and their expression finely tunes cell responses. Human γδ T cells express several NKRs. Expression of these receptors is confined to the cytolytic Vδ2 subset, which coexpresses the FcγRIII CD16 and CD45RA and has been defined as Vγ9Vδ2 T(EMRA) cells. We show that the CD94/NKG2C complex, associated with KARAP/DAP12, is fully functional in γδ T cells, as determined by measuring IFN-γ production, T cell proliferation, and cytolytic activity by γδ lymphocytes. In contrast, NKG2A expression was found on all γδ T cell memory subsets, suggesting a crucial role of the inhibitory signal provided by this receptor on γδ T cell responses. Moreover, we found Vγ9Vδ2 T(EMRA), NK, and CD8+ αβ T cells coexpressing NKG2A and NKG2C receptors. Functional experiments showed that the inhibitory signal mediated by the NKG2A receptor prevails when double-positive cells are activated. Finally, NKG2A expression on γδ LDGL correlates with asymptomatic pathology, even in the presence of NKG2C coexpression, whereas in symptomatic patients affected by severe disease, the inhibitory NKG2A receptor is absent, and a variety of activatory NKRs was found. We propose that the silent behavior of γδ cells in LDGL patients is a result of effective inhibitory HLA class I receptors.

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“…CD56 + NK cells have been known to represent a highly specialized lymphoid population characterized by a potent cytolytic activity against tumor or virally infected cells [32]. Compared to healthy controls, the cytotoxicity of NK cells decreases in peripheral blood of patients with various types of cancer [33].…”

Section: Resultsmentioning

confidence: 99%

A Screening Platform for Compounds with Potential Immuno-Regulatory Activities Using Human Cord Blood Mononuclear Cells

Chen¹,

Tsai²,

Hsieh³

et al. 2006

CCHTS

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A systematic and combinatorial approach was adopted using human umbilical cord blood mononuclear cells (hUCB-MNCs) to screen for potential immuno-regulatory compounds. The hUCB-MNCs contain several types of immunogenic cells, which are a suitable material to mimic the in vivo immuno-response after drug treatment. hUCB-MNCs were treated with various natural products such as quercetin, astaxanthin, caffeic acid, bilobalide, eugenol, rutin and gamma-dodecalactone (gamma-DDL). Phenotypic expression analysis revealed that the subpopulation of CD3(+) T cells, CD56(+) NK cells and CD1a(+) dendritic cells apparently increased after being treated with gamma-DDL for 6 days. The expression of CD56 reached a maximum at 72 h with a dose-dependent relationship. The NK cells activation marker (CD69) also elevated following gamma-DDL treatment. These results demonstrated that the gamma-DDL has immuno-regulatory effects to enhance cord blood NK cells population and bioactivities. Such a high-throughput methodology using hUCB-MNCs may be an effective platform for systematically screening potential immuno-regulatory compounds.

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Functional inhibitory human leucocyte antigen class I receptors on natural killer (NK) cells in patients with chronic NK lymphocytosis

Cited by 14 publications

References 48 publications

Characteristic expansion of CD45RA⁺ CD27⁻ CD28⁻ CCR7⁻ lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

Characteristic expansion of CD45RA⁺ CD27⁻ CD28⁻ CCR7⁻ lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease

A Screening Platform for Compounds with Potential Immuno-Regulatory Activities Using Human Cord Blood Mononuclear Cells

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Functional inhibitory human leucocyte antigen class I receptors on natural killer (NK) cells in patients with chronic NK lymphocytosis

Cited by 14 publications

References 48 publications

Characteristic expansion of CD45RA+ CD27− CD28− CCR7− lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

Characteristic expansion of CD45RA+ CD27− CD28− CCR7− lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease

A Screening Platform for Compounds with Potential Immuno-Regulatory Activities Using Human Cord Blood Mononuclear Cells

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Product

Resources

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Characteristic expansion of CD45RA⁺ CD27⁻ CD28⁻ CCR7⁻ lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes

Characteristic expansion of CD45RA⁺ CD27⁻ CD28⁻ CCR7⁻ lymphocytes with stable natural killer (NK) receptor expression in NK‐ and T‐cell type lymphoproliferative disease of granular lymphocytes