Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness

Emma Guttman-Yassky, Yulia Vugmeyster, Michelle A. Lowes, Francesca Chamian, Toyoko Kikuchi, Mark Kagen, Patricia Gilleaudeau, Edmund Lee, Brisdell Hunte, Kathy Howell, Wolfgang Dummer, Sarah C. Bodary, James G. Krueger

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Efalizumab (anti-CD11a) interferes with LFA-1/ICAM-1 binding and inhibits several key steps in psoriasis pathogenesis. This study characterizes the effects of efalizumab on T-cell activation responses and expression of surface markers on human circulating psoriatic T cells during a therapeutic trial. Our data suggest that efalizumab may induce a unique type of T-cell hyporesponsiveness, directly induced by LFA-1 binding, which is distinct from conventional anergy described in animal models. Direct activation of T cells through different activating receptors (CD2, CD3, CD3/28) is reduced, despite T cells being fully viable. This hyporesponsiveness was spontaneously reversible after withdrawal of the drug, and by IL-2 in vitro. In contrast to the state of anergy, Ca+2 release is intact during efalizumab binding. Furthermore, lymphocyte function-associated antigen-1 (LFA-1) blockade resulted in an unexpected downregulation of a broad range of surface molecules, including the T-cell receptor complex, co-stimulatory molecules, and integrins unrelated to LFA-1, both in the peripheral circulation and in diseased skin tissue. These observations provide evidence for the mechanism of action of efalizumab. The nature of this T-cell hyporesponsiveness suggests that T-cell responses may be reduced during efalizumab therapy, but are reversible after ceasing efalizumab treatment.

Original languageEnglish (US)
Pages (from-to)1182-1191
Number of pages10
JournalJournal of Investigative Dermatology
Volume128
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

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T-cells
Psoriasis
Lymphocyte Function-Associated Antigen-1
T-Lymphocytes
Chemical activation
Molecules
Intercellular Adhesion Molecule-1
T-Cell Antigen Receptor
efalizumab
Skin Diseases
Integrins
Interleukin-2
Skin
Animals
Therapeutics
Down-Regulation
Animal Models
Tissue
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Dermatology

Cite this

Guttman-Yassky, E., Vugmeyster, Y., Lowes, M. A., Chamian, F., Kikuchi, T., Kagen, M., ... Krueger, J. G. (2008). Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness. Journal of Investigative Dermatology, 128(5), 1182-1191. https://doi.org/10.1038/jid.2008.4

Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness. / Guttman-Yassky, Emma; Vugmeyster, Yulia; Lowes, Michelle A.; Chamian, Francesca; Kikuchi, Toyoko; Kagen, Mark; Gilleaudeau, Patricia; Lee, Edmund; Hunte, Brisdell; Howell, Kathy; Dummer, Wolfgang; Bodary, Sarah C.; Krueger, James G.

In: Journal of Investigative Dermatology, Vol. 128, No. 5, 05.2008, p. 1182-1191.

Research output: Contribution to journalArticle

Guttman-Yassky, E, Vugmeyster, Y, Lowes, MA, Chamian, F, Kikuchi, T, Kagen, M, Gilleaudeau, P, Lee, E, Hunte, B, Howell, K, Dummer, W, Bodary, SC & Krueger, JG 2008, 'Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness', Journal of Investigative Dermatology, vol. 128, no. 5, pp. 1182-1191. https://doi.org/10.1038/jid.2008.4
Guttman-Yassky, Emma ; Vugmeyster, Yulia ; Lowes, Michelle A. ; Chamian, Francesca ; Kikuchi, Toyoko ; Kagen, Mark ; Gilleaudeau, Patricia ; Lee, Edmund ; Hunte, Brisdell ; Howell, Kathy ; Dummer, Wolfgang ; Bodary, Sarah C. ; Krueger, James G. / Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness. In: Journal of Investigative Dermatology. 2008 ; Vol. 128, No. 5. pp. 1182-1191.
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