Psoriasis Research Today is a free monthly online journal that collates and summarizes the latest research about Psoriasis, including details on treatment, prevention, medication, causes.

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

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

Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10065, USA.

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.

Published 14 April 2008 in J Invest Dermatol, 128(5): 1182-91.
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