T Cells and T Cell-Derived Cytokines as Pathogenic Factors in the Nonallergic Form of Atopic Dermatitis

Abstract

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.

T cell–mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis

“…Acute lesions and early response after epidermal allergen application were characterized with a predominant type 2 cytokine pattern (4,16,57). Increased levels of IL-12 mRNA was demonstrated in chronic AD lesions (58), and chronic lesions were characterized by increased IFN-γ and decreased IL-4 levels, with more or less constant IL-5 and IL-13 levels (13,15,16,57,58). We observed killing of KCs by type 2 T cells after stimulation in the presence of IL-12.…”

“…T cells appear to be important players regulating inflammatory processes in eczematous dermatitis (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). This is supported by the observation that immunosuppressive drugs such as FK-506 and glucocorticoids, which block T-cell activation, are effective in treatment of eczematous disorders (4,5).…”

Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

“…role in allergic eczema formation (29,31). Moreover, recent reports demonstrated that transgenic mice expressing caspase 1 in keratinocytes spontaneously developed AD-like skin disease with an elevation of the active form of IL-18 in serum (37).…”

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity

“…Over 80% of patients with atopic dermatitis (AD) have increased IgEs to foods and inhalant allergens in the peripheral blood (43). However, the positive predictive value of IgE specific to food allergens is low (44).…”