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

47 Scopus citations


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
Issue number5
StatePublished - May 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness'. Together they form a unique fingerprint.

  • Cite this

    Guttman-Yassky, E., Vugmeyster, Y., Lowes, M. A., Chamian, F., Kikuchi, T., Kagen, M., Gilleaudeau, P., Lee, E., Hunte, B., Howell, K., Dummer, W., Bodary, S. C., & 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.