The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.

Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.

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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 cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2-biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte-associated antigen-bearing (CLA+) CD45RO+ T cells with skin-specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation-induced apoptosis. The freshly purified CLA+ CD45RO+ T cells of atopic individuals display distinct features of in vivo-triggered apoptosis such as pro-caspase degradation and active caspase-8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation-induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non-atopic patients such as psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases.