Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris.
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.
Chamian
Francesca
F
Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10021.
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
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*
D015703:Antigens, CD; D011993:Recombinant Fusion Proteins; D000077944:Alefacept