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

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 2004
Externally publishedYes

Fingerprint

Psoriasis
Leukocytes
T-Lymphocytes
Skin
Lymphocytes
Leukocyte Count
Population
Antibodies, Monoclonal, Humanized
Lymphocyte Function-Associated Antigen-1
T-Lymphocyte Subsets
Therapeutics
Integrins
efalizumab
Blood Cells
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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

In: Clinical Immunology, Vol. 113, No. 1, 10.2004, p. 38-46.

Research output: Contribution to journalArticle

Vugmeyster, Y, Kikuchi, T, Lowes, MA, Chamian, F, Kagen, M, Gilleaudeau, P, Lee, E, Howell, K, Bodary, S, Dummer, W & Krueger, JG 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, vol. 113, no. 1, pp. 38-46. https://doi.org/10.1016/j.clim.2004.06.001
Vugmeyster, Yulia ; Kikuchi, Toyoko ; Lowes, Michelle A. ; Chamian, Francesca ; Kagen, Mark ; Gilleaudeau, Patricia ; Lee, Edmund ; Howell, Kathy ; Bodary, Sarah ; Dummer, Wolfgang ; Krueger, James G. / 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. In: Clinical Immunology. 2004 ; Vol. 113, No. 1. pp. 38-46.
@article{be7a03b9132545cabdb4a82c098e7b6b,
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-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.",
keywords = "anti-CD11a, Auto-immune response, CD11a, Inflammation, LFA-1, Monoclonal antibody, Psoriasis, T cells",
author = "Yulia Vugmeyster and Toyoko Kikuchi and Lowes, {Michelle A.} and Francesca Chamian and Mark Kagen and Patricia Gilleaudeau and Edmund Lee and Kathy Howell and Sarah Bodary and Wolfgang Dummer and Krueger, {James G.}",
year = "2004",
month = "10",
doi = "10.1016/j.clim.2004.06.001",
language = "English (US)",
volume = "113",
pages = "38--46",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - 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

AU - Vugmeyster, Yulia

AU - Kikuchi, Toyoko

AU - Lowes, Michelle A.

AU - Chamian, Francesca

AU - Kagen, Mark

AU - Gilleaudeau, Patricia

AU - Lee, Edmund

AU - Howell, Kathy

AU - Bodary, Sarah

AU - Dummer, Wolfgang

AU - Krueger, James G.

PY - 2004/10

Y1 - 2004/10

N2 - 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.

AB - 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.

KW - anti-CD11a

KW - Auto-immune response

KW - CD11a

KW - Inflammation

KW - LFA-1

KW - Monoclonal antibody

KW - Psoriasis

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=6044227840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6044227840&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2004.06.001

DO - 10.1016/j.clim.2004.06.001

M3 - Article

VL - 113

SP - 38

EP - 46

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 1

ER -