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.

Authors:
Yulia Vugmeyster
Yulia Vugmeyster
Harvard Medical School
United States
Toyoko Kikuchi
Toyoko Kikuchi
The Rockefeller University
United States
Michelle A Lowes
Michelle A Lowes
The Rockefeller University
United States
Francesca Chamian
Francesca Chamian
Laboratory for Investigative Dermatology
Mark Kagen
Mark Kagen
University Hospitals of Cleveland/Case Western Reserve University
United States
Patricia Gilleaudeau
Patricia Gilleaudeau
The Rockefeller University
United States
Edmund Lee
Edmund Lee
Rutgers New Jersey Medical School
United States
Kathy Howell
Kathy Howell
The Rockefeller University
United States

Clin Immunol 2004 Oct;113(1):38-46

Genentech, Inc., South San Francisco, CA, USA.

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.

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Source
http://dx.doi.org/10.1016/j.clim.2004.06.001DOI Listing
October 2004
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