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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 113; no. 1; pp. 38 - 46
• Main Authors: Vugmeyster, Yulia, Kikuchi, Toyoko, Lowes, Michelle A., Chamian, Francesca, Kagen, Mark, Gilleaudeau, Patricia, Lee, Edmund, Howell, Kathy, Bodary, Sarah, Dummer, Wolfgang, Krueger, James G.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.2004; Elsevier
• Subjects: anti-CD11a; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Auto-immune response; Biological and medical sciences; CD11a; CD11a Antigen - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Adhesion - drug effects; Cell Adhesion - immunology; Cell Adhesion Molecules - drug effects; Cell Adhesion Molecules - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunologic Memory - drug effects; Immunologic Memory - immunology; Immunopathology; Inflammation; LFA-1; Medical sciences; Monoclonal antibody; Psoriasis; Psoriasis - drug therapy; Psoriasis - immunology; T cells; Psoriasis; LFA-1; Auto-immune response; anti-CD11a; Inflammation; Monoclonal antibody; T cells; CD11a; Human; Immunopathology; Skin disease; Immune response; Leukocyte; Efalizumab; Blood; Memory lymphocyte; Immunomodulator; Immunology; T-Lymphocyte
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2004.06.001

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-γ 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 β7 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.