title: Expression and function of the natural cytotoxicity receptor NKp46 on circulating malignant CD4+ T lymphocytes of Sézary syndrome patients.
abstract: The natural cytotoxicity receptors NKp30, NKp44, and NKp46 were identified as activating receptors mainly expressed by natural killer (NK) lymphocytes. In this study we show that peripheral blood malignant CD4(+) T lymphocytes from patients with Sézary syndrome, an aggressive form of cutaneous T-cell lymphoma, express NKp46 at their cell surface. Although NKp46 does not behave as an independent functional receptor, its engagement provides a strong inhibiting signal on the malignant T lymphocyte CD3-induced proliferation. We show that this inhibition is correlated with a decreased phosphorylation of the CD3ζ chain associated with NKp46 and/or the TCR/CD3 complexes. Our results reveal that in addition to KIR3DL2/CD158k expression, NKp46 could represent an additional marker on the circulating malignant T lymphocytes of Sézary patients, where it displays an as yet unreported function of inhibitory co-receptor able to interfere with the processes governing their CD3-dependent proliferation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U976, Hôpital Saint Louis, Paris, France [2] Université Denis Diderot-Paris 7, Paris, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Natacha
authors.initials: N
authors.lastname: Remtoula
authors.forename: Simona
authors.initials: S
authors.lastname: Sivori
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Anne
authors.initials: A
authors.lastname: Marie-Cardine
mesh_terms: D014408:Biomarkers, Tumor; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002455:Cell Division / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics* / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000235:genetics / Q000378:metabolism; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000378:metabolism; D012751:Sezary Syndrome / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor; D017252:CD3 Complex; C515077:KIR2DL2 protein, human; C515083:KIR3DL1 protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D054343:Receptors, KIR2DL2; D054341:Receptors, KIR3DL1