title: Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris.
abstract: Psoriasis vulgaris, a skin disease that is considered to be the result of a type 1 autoimmune response, provides an opportunity for studying the changes that occur in a target-diseased tissue during innovative immunotherapies. To gain a more comprehensive picture of the response to an approved biological therapy, we studied alfacept, which is a CD2 binding fusion protein. We examined T cells, dendritic cells (DCs), and expression of a number of inflammatory genes. In 22 patients, 55% demonstrated a clear histological remission of the disease, with a 73% reduction in lesional lymphocytes and a 79% decrease in infiltrating CD8+ cells. Only histological responders showed marked reductions in the tissue expression of inflammatory genes IFN-gamma, signal transducer and activator of transcription 1, monokine induced by IFN-gamma, inducible NO synthase, IL-8, and IL-23 subunits. Parallel decreases in CD83+ and CD11c+ DCs also were measured by immunohistochemistry. Because we observed that alefacept binds primarily to T cells and not DCs, we suggest that T cells are the primary target for therapy, but that DCs and a spectrum of type 1 inflammatory genes are coordinately suppressed.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10021.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chamian
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: Shao-Lee
authors.initials: SL
authors.lastname: Lin
authors.forename: Edmund
authors.initials: E
authors.lastname: Lee
authors.forename: Toyoko
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Artemis
authors.initials: A
authors.lastname: Khatcherian
authors.forename: Inna
authors.initials: I
authors.lastname: Novitskaya
authors.forename: Knut M
authors.initials: KM
authors.lastname: Wittkowski
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000328:Adult; D000368:Aged; D000077944:Alefacept; D015703:Antigens, CD / Q000276:immunology; D001706:Biopsy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D011993:Recombinant Fusion Proteins; D000077944:Alefacept