Nonspecific T-cell homing during inflammation in atopic dermatitis: Expression of cutaneous lymphocyte-associated antigen and integrin αEβ7 on skin-infiltrating T cells,☆☆,,★★

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Abstract

Atopic dermatitis (AD) is a chronic skin disorder, characterized by infiltration of activated memory CD4+ T cells into skin. A model to study the onset of allergic inflammation in a patient with AD is the atopy patch test (APT), in which, by epicutaneous application of aeroallergen, an eczematous reaction is induced in 50% of sensitized patients with AD. Extravasation of T cells into skin is thought to be critically dependent on expression of the surface molecule cutaneous lymphocyte-associated antigen (CLA), which recognizes and binds its ligand E-selectin on endothelium. We studied the dynamics of expression of CLA and the gut homing receptor αEβ7 (HML-1) on T cells in the skin of patients with AD and in APT reactions and nickel and sodium lauryl sulfate patch test reactions by means of immunohistochemical double staining of skin biopsy specimens. The results show an increase in the number of CD3+ T cells in the lesional skin of patients with AD, APT reactions, and nickel and sodium lauryl sulfate patch test reactions as compared with nonlesional skin of the same patients and nonatopic individuals. In contrast, the percentages of CLA+ T cells in the lesional skin of patients with AD, in the APT reactions, and in sodium lauryl sulfate and nickel patch test reactions were decreased. In addition, we found a marked expression of αEβ7 by T cells present in skin, indicating a nonspecific influx of T cells during allergic skin inflammation. We propose that during allergic skin inflammation CLA expression is not a prerequisite for cutaneous T-cell infiltration. CLA expression may be important for T cells to extravasate from blood into skin during immune surveillance or for retention of allergen-specific T cells in skin. (J Allergy Clin Immunol 1997;100:694-701.)

Section snippets

Patients with AD

We studied 16 patients with AD, diagnosed according to the criteria of Hanifin and Rajka,19 who were selected on the demonstration of a positive APT response at 24 hours, a positive skin prick test response (defined as >3 mm induration 20 minutes after intradermal allergen challenge), and a positive RAST response to house dust mite allergen. APTs were performed as described previously.16 In short, clinically noninvolved skin of the back was stripped 10 times with adhesive tape, after which

Increased numbers of CD3+ cells in lesional and clinically noninvolved skin of patients with AD

Skin biopsy specimens from nonatopic control subjects and patients with AD were immunohistochemically stained for the pan-T cell marker CD3. In lesional skin of patients with AD, the number of CD3+ cells was significantly increased when compared with clinically noninvolved skin of patients with AD, which in turn contained significantly higher numbers of CD3+ cells than skin of nonatopic subjects (Table I).

Higher percentage of CLA+ T cells in clinically noninvolved skin of patients with AD than in lesional skin of patients with AD

To study the expression of homing receptors on T cells in skin of patients with AD and

Discussion

To perform their effector and immunoregulatory functions, T cells must extravasate from blood into tissue. A specific mechanism by which T cells extravasate is called selective homing. In this process T cells expressing homing receptors are able to migrate from blood into discrete tissue sites by local expression of homing receptor ligands on vascular endothelium. This concept is based on the observation that under normal, noninflammatory conditions, the expression of homing receptors on T

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    From the Department of Dermatology-Allergology, University Hospital Utrecht, Utrecht.

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    Supported by the Dutch Asthma Foundation, grant 32.91.55.

    Reprint requests: I. Jolanda M. de Vries, Department of Dermatology-Allergology G02.124, University Hospital Utrecht, Postbus 85500, NL-3508 GA Utrecht, The Netherlands.

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