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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.

SUBMITTER: Chamian F 

PROVIDER: S-EPMC545584 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

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Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris.

Chamian Francesca F   Lowes Michelle A MA   Lin Shao-Lee SL   Lee Edmund E   Kikuchi Toyoko T   Gilleaudeau Patricia P   Sullivan-Whalen Mary M   Cardinale Irma I   Khatcherian Artemis A   Novitskaya Inna I   Wittkowski Knut M KM   Krueger James G JG  

Proceedings of the National Academy of Sciences of the United States of America 20050125 6


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% demonstrate  ...[more]

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