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Recently we have shown that T-cell-mediated keratinocyte apoptosis plays a key pathogenetic role in the formation of eczematous dermatitis. Spongiosis, the histologic hallmark of eczematous dermatitis, is characterized by impairment of cohesion between epidermal keratinocytes. It is conceivable that the intercellular junction of keratinocytes is an early target of apoptosis-inducing T cells. In this study, we demonstrate that the induction of keratinocyte apoptosis is accompanied by a rapid cleavage of E-cadherin and loss of coimmunoprecipitated beta-catenin. In situ examination of E-cadherin expression and cellular distribution in acute eczematous dermatitis revealed a reduction in keratinocyte membrane E-cadherin in areas of spongiosis. In contrast, the in vitro and in vivo expression of desmosomal cadherins during early apoptosis remained unchanged. Therefore, induction of keratinocyte apoptosis by skin-infiltrating T cells, subseqent cleavage of E-cadherin, and resisting desmosomal cadherins suggests a mechanism for spongiosis formation in eczematous dermatitis.

A subgroup of patients with atopic dermatitis are known to have normal serum total immunoglobulin E levels, undetectable specific immunoglobulin E, and negative skin prick tests towards allergens. This form of the disease has been termed nonallergic atopic dermatitis. In this study, we found that, among 1151 chronic atopic dermatitis patients, about 10% had normal serum immunoglobulin E levels with no evidence for immunoglobulin E sensitization. We investigated immunologic mechanisms of patients with "allergic" and "nonallergic" atopic dermatitis using peripheral blood and skin biopsy samples. Our data suggest that T cells are likely involved in the pathogenesis of both forms of atopic dermatitis. Skin T cells equally responded to superantigen, staphylococcal enterotoxin B, and produced interleukin-2, interleukin-5, interleukin-13, and interferon-gamma in both forms of the disease. Interleukin-4, however, was not detectable in the skin biopsies of both atopic dermatitis types and was secreted in very low amounts by T cells cultured from the skin biopsies. Moreover, skin T cells from nonallergic atopic dermatitis patients expressed lower interleukin-5 and interleukin-13 levels compared with allergic atopic dermatitis patients. Accordingly, T cells isolated from skin biopsies of atopic dermatitis, but not from the nonallergic atopic dermatitis, induced high immunoglobulin E production in cocultures with normal B cells that was mediated by interleukin-13. In addition, B cell activation with high CD23 expression was observed in the peripheral blood of atopic dermatitis, but not nonallergic atopic dermatitis patients. These data suggest, although high numbers of T cells are present in lesional skin of both types, a lack of interleukin-13-induced B cell activation and consequent immunoglobulin E production in nonallergic atopic dermatitis.