title: Membrane expression of NK receptors CD160 and CD158k contributes to delineate a unique CD4+ T-lymphocyte subset in normal and mycosis fungoides skin.
abstract: CD160 is a GPI-anchored Ig-like receptor identified by the BY55 mAb on human circulating CD56dim+ NK cells and TCRγδ lymphocytes. In addition, while most intestinal T lymphocytes express it, only a minor circulating CD4+ or CD8+ T lymphocyte subset is CD160+. Here we describe a population of CD4+ CD160+ human blood T lymphocytes of circulating cutaneous T cells. These rare T lymphocytes represent 2.1 ± 1.9% of the circulating CD3+ CD4+ T cells, coexpress CD8αα, CD244, and perforin but lack CD28 expression, a phenotype corresponding to effector memory cytotoxic T-lymphocytes. Functional studies further confirmed their cytotoxic potential. These cells lack αEβ7 integrin and CCR7 expression but do express skin-addressing molecules CLA, and CCR4. In normal human skin, CD4+ CD160+ cells represent 34.6 ± 14.7% of the CD4+ T lymphocytes extracted by collagenase treatment. These T cells coexpress CLA (81 ± 13.6%), CCR4 (62.3 ± 15.9%), and some CD8αα (19.6 ± 13%) or CCR7 (24.4 ± 11.7%) expression. Cutaneous T-cell lymphoma cells express the natural killer receptor KIR3DL2 (CD158k) used as a tumor marker. Not only we confirmed the expression of this marker in the blood and/or skin of mycosis fungoides patients but we also show for the first time CD158k expression (often associated with CD160) on cutaneous CD4+ T cells from healthy individuals (25.3 ± 15%). Therefore, CD4+ CD160+ T cells expressing CD158k might represent specialized cutaneous lymphocytes devoted to immune surveillance, from which could originate cutaneous T-cell lymphomas such as mycosis fungoides.
authors.affiliation: INSERM, U976, F-75010, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, UMR-S 976, F-75739, Paris, France.
authors.forename: Nouhoum
authors.initials: N
authors.lastname: Sako
authors.forename: Valérie
authors.initials: V
authors.lastname: Schiavon
authors.forename: Touda
authors.initials: T
authors.lastname: Bounfour
authors.forename: Valérie
authors.initials: V
authors.lastname: Dessirier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Caroline
authors.initials: C
authors.lastname: Ram-Wolff
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel
authors.forename: Hélène
authors.initials: H
authors.lastname: Sicard
authors.forename: Anne
authors.initials: A
authors.lastname: Marie-Cardine
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Christian
authors.initials: C
authors.lastname: Schmitt
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008297:Male; D009182:Mycosis Fungoides / Q000175:diagnosis / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D054343:Receptors, KIR2DL2 / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; C515077:KIR2DL2 protein, human; D011971:Receptors, Immunologic; D054343:Receptors, KIR2DL2
keywords: BY55; CD158k; CD160; KIR3DL2; mycosis fungoides; skin lymphocytes