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

Yulia Vugmeyster, Toyoko Kikuchi, Michelle A. Lowes, Francesca Chamian, Mark Kagen, Patricia Gilleaudeau, Edmund Lee, Kathy Howell, Sarah Bodary, Wolfgang Dummer, James G. Krueger

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73 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalClinical Immunology
Volume113
Issue number1
DOIs
StatePublished - Oct 1 2004

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Keywords

  • Auto-immune response
  • CD11a
  • Inflammation
  • LFA-1
  • Monoclonal antibody
  • Psoriasis
  • T cells
  • anti-CD11a

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Vugmeyster, Y., Kikuchi, T., Lowes, M. A., Chamian, F., Kagen, M., Gilleaudeau, P., Lee, E., Howell, K., Bodary, S., Dummer, W., & Krueger, J. G. (2004). 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. Clinical Immunology, 113(1), 38-46. https://doi.org/10.1016/j.clim.2004.06.001