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Titolo:
The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+T-cells in asthma
Autore:
Kon, OM; Sihra, BS; Loh, LC; Barkans, J; Compton, CH; Barnes, NC; Larche, M; Kay, AB;
Indirizzi:
Univ London Imperial Coll Sci Technol & Med, Sch Med, Natl Heart & Lung Inst, Dept Allergy & Clin Immunol, London SW3 6LY, England Univ London Imperial Coll Sci Technol & Med London England SW3 6LY gland SmithKline Beecham Pharmaceut, Harlow CM19 5AD, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AD ssex, England London Chest Hosp, London E2 9JX, England London Chest Hosp London England E2 9JX est Hosp, London E2 9JX, England
Titolo Testata:
EUROPEAN RESPIRATORY JOURNAL
fascicolo: 1, volume: 18, anno: 2001,
pagine: 45 - 52
SICI:
0903-1936(200107)18:1<45:TEOAAM>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN T-CELLS; HUMAN CD4; CHIMERIC ANTIBODY; DISEASE SEVERITY; LYMPHOCYTES-T; ATOPIC ASTHMA; IN-VIVO; EOSINOPHILIA; EXPRESSION; APOPTOSIS;
Keywords:
anti-CD4; asthma; cytokine; flow-cytometry; monoclonal antibody; proliferation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Kay, AB Univ London Imperial Coll Sci Technol & Med, Sch Med, Natl Heart &Lung Inst, Dept Allergy & Clin Immunol, Dovehouse St, London SW3 6LY, England Univ London Imperial Coll Sci Technol & Med Dovehouse St London England SW3 6LY
Citazione:
O.M. Kon et al., "The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+T-cells in asthma", EUR RESP J, 18(1), 2001, pp. 45-52

Abstract

CD4+ T-cells are likely to be involved as a source of pro-inflammatory cytokines in asthma. This study assessed the effects of an infusion of keliximab (IDEC CE9.1), an anti-CD4+ monoclonal antibody, on peripheral blood CD4T-cells in corticosteroid-dependent asthmatics. Three cohorts of patients (termed C0.5: n=6, C1.5: n=5, and C3.0: n=5) received a single infusion of 0.5, 1.5 or 3.0 mg.kg(-1), respectively, with a fourth receiving placebo (Cpi: n=6), and were followed-up for 4 weeks. By flow cytometry in peripheral blood, pre- and postinfusion assessment was made of. a) CD4 and CD8 counts and mean fluorescence; b) CD25, human leukocyteantigen-DR (HLA-DR), CD45RO and CD45RA expression on CD4+ T-cells; and c) interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 expression in CD4+ T-cells. Keliximab's in vitro effects on allergen-specific peripheral blood mononuclear cells (PBMC) proliferation in atopic asthmatics were also evaluated. There was a significant increase in lung function (peak expiratory flow rate) in the C3.0 group. Following infusion in C0.5, C1.5 and C3.0 but not Cpl: 1) the CD4, but not CD8 count was significantly decreased; 2) there was total loss of Leu3a staining; 3) there were significant reductions in the mean fluorescence of OKT4 binding; and 4) there were significant reductions in the numbers of CD25, HLA-DR, CD45RO and CD45RA/CD4+ cells. There were nochanges in CD4+ cell expression of IFN-gamma, IL-4 or IL-5. Keliximab caused a significant reduction in T-cell proliferation as compared to a controlmonoclonal antibody. Keliximab, as an anti-CD4 monoclonal antibody, leads to a transient reduction in the number of CD4+ T-cells and modulation of CD4+ receptor expression in severe asthmatics. The effects of keliximab may be mediated through a decrease in CD4+ surface expression and T-lymphocyte numbers, in addition to a reduction in allergen-induced proliferation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 20:40:26