{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:41:37Z","timestamp":1779183697931,"version":"3.51.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alefacept is an LFA3-Ig fusion protein that binds to CD2 and is thought to inhibit T cell activation by antagonism of CD2 signaling or by lysis of CD2+ cells. Alefacept is potential future therapeutic for organ transplant recipients or graft-vs-host disease and is an approved therapeutic for psoriasis vulgaris, which is a T cell-mediated inflammatory disease. However, alefacept improves psoriasis in only \u223c50% of patients treated for 12 wk. We studied the immunologic effects of alefacept in a group of psoriasis patients during treatment. We found that T cells, especially CD8+ T cells, were rapidly decreased in the peripheral circulation. Decreases in circulating T cells were not associated with induced apoptosis. Unexpectedly, in addition to suppression of inflammatory genes, we found a marked induction of mRNAs for STAT1, IL-8, and monokine induced by IFN-\u03b3 during the first day of treatment in PBMC. We confirmed the agonistic effects of alefacept in PBMC in vitro, which were similar to CD3\/CD28 ligation on T cells. These data establish that alefacept activates gene expression programs in leukocytes and suggest that its therapeutic action may be as a mixed agonist\/antagonist. Furthermore, responding patients to alefacept treatment show unique patterns of gene modulation. Whereas alefacept down-regulated TCRs CD3D and CD2 in responders, nonresponders reveal a higher expression of T cell activation genes such as CD69 in pretreatment PBMC. These finding suggest a potential basis for categorizing responders vs nonresponders at an early time point in treatment or before treatment of a broad range of proinflammatory diseases. This study 1) establishes alefacept as a novel CD2 agonist molecule for induction of leukocyte activation genes (prior work proposed its mechanism as a CD2 antagonist) and 2) that differential activation of genes may categorize clinical responders to this agent, critical for cost-effective use of this drug.<\/jats:p>","DOI":"10.4049\/jimmunol.178.11.7442","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:24:11Z","timestamp":1397863451000},"page":"7442-7449","source":"Crossref","is-referenced-by-count":47,"title":["Novel Insight into the Agonistic Mechanism of Alefacept In Vivo: Differentially Expressed Genes May Serve as Biomarkers of Response in Psoriasis Patients"],"prefix":"10.1093","volume":"178","author":[{"given":"Asifa S","family":"Haider","sequence":"first","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A","family":"Lowes","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humphrey","family":"Gardner","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, MA 02142"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj","family":"Bandaru","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, MA 02142"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamruz","family":"Darabi","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Chamian","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toyoko","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Gilleaudeau","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary S","family":"Whalen","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma","family":"Cardinale","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna","family":"Novitskaya","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G","family":"Krueger","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, Rockefeller University , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,6,1]]},"reference":[{"key":"2025032803190269100_R1","first-page":"2004","volume-title":"N. 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