title: Efalizumab (anti-CD11a)-induced increase in peripheral blood leukocytes in psoriasis patients is preferentially mediated by altered trafficking of memory CD8+ T cells into lesional skin.
abstract: Therapeutic administration of efalizumab, a humanized antibody to CD11a, induces a marked but reversible increase of peripheral lymphocytes in psoriasis patients. In this study, 13 patients were treated with 12 weekly subcutaneous doses (2 mg/kg/week) of efalizumab, and all 13 patients had increases in leukocyte counts. This increased white blood cell count was mainly due to a 3- to 4-fold increase in the number of circulating CD3(+) lymphocytes during active treatment. Both naive and memory populations of CD4(+) and CD8(+) lymphocytes in the peripheral blood increased, with the largest increase observed in memory CD8(+) T cells. This CD8(+) memory T cell subset is a prominent T cell population found in psoriatic skin. An increase in Type 1 (IFN-gamma producing) T cells was also observed during treatment. Both components of LFA-1, CD11a and CD18, were downregulated during treatment, and surprisingly the integrins CD11b and beta 7 were similarly reduced. We conclude that efalizumab most likely blocks cutaneous entry of memory CD8(+) T cells, a highly disease-relevant cell population. The relatively smaller increase in naive peripheral blood T cells could be attributed to reduced trafficking of naive T cells.
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Vugmeyster
authors.forename: Toyoko
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: Francesca
authors.initials: F
authors.lastname: Chamian
authors.forename: Mark
authors.initials: M
authors.lastname: Kagen
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: Edmund
authors.initials: E
authors.lastname: Lee
authors.forename: Kathy
authors.initials: K
authors.lastname: Howell
authors.forename: Sarah
authors.initials: S
authors.lastname: Bodary
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dummer
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen; D015815:Cell Adhesion Molecules; C472181:efalizumab