title: Phenotypic studies of natural killer cell subsets in human transporter associated with antigen processing deficiency.
abstract: Peripheral blood natural killer (NK) cells from patients with transporter associated with antigen processing (TAP) deficiency are hyporesponsive. The mechanism of this defect is unknown, but the phenotype of TAP-deficient NK cells is almost normal. However, we noticed a high percentage of CD56(bright) cells among total NK cells from two patients. We further investigated TAP-deficient NK cells in these patients and compared them to NK cells from two other TAP-deficient patients with no clinical symptoms and to individuals with chronic inflammatory diseases other than TAP deficiency (chronic lung diseases or vasculitis). Peripheral blood mononuclear cells isolated from venous blood were stained with fluorochrome-conjugated antibodies and the phenotype of NK cells was analyzed by flow cytometry. In addition, (51)Chromium release assays were performed to assess the cytotoxic activity of NK cells. In the symptomatic patients, CD56(bright) NK cells represented 28% and 45%, respectively, of all NK cells (higher than in healthy donors). The patients also displayed a higher percentage of CD56(dim)CD16(-) NK cells than controls. Interestingly, this unusual NK cell subtype distribution was not found in the two asymptomatic TAP-deficient cases, but was instead present in several of the other patients. Over-expression of the inhibitory receptor CD94/NKG2A by TAP-deficient NK cells was confirmed and extended to the inhibitory receptor ILT2 (CD85j). These inhibitory receptors were not involved in regulating the cytotoxicity of TAP-deficient NK cells. We conclude that expansion of the CD56(bright) NK cell subtype in peripheral blood is not a hallmark of TAP deficiency, but can be found in other diseases as well. This might reflect a reaction of the immune system to pathologic conditions. It could be interesting to investigate the relative distribution of NK cell subsets in various respiratory and autoimmune diseases.
authors.affiliation: Laboratoire d'Immunogénétique-Allergologie, Centre de Recherche Public de la Santé, Luxembourg City, Luxembourg. jacques.zimmer@crp-sante.lu
authors.forename: Jacques
authors.initials: J
authors.lastname: Zimmer
authors.forename: Huguette
authors.initials: H
authors.lastname: Bausinger
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Andrès
authors.forename: Lionel
authors.initials: L
authors.lastname: Donato
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: François
authors.initials: F
authors.lastname: Hentges
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Henri
authors.initials: H
authors.lastname: de la Salle
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000502:physiology*; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000097:blood; D001692:Biological Transport; D019002:CD56 Antigen / Q000096:biosynthesis; D002860:Chromium Radioisotopes; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D017452:Receptors, IgG / Q000096:biosynthesis
chemical_list: D018528:ATP-Binding Cassette Transporters; D019002:CD56 Antigen; D002860:Chromium Radioisotopes; D017452:Receptors, IgG; C477327:transporter associated with antigen processing (TAP)