Prominent Involvement of Activated Th1-Subset of T-Cells and Increased Expression of Receptor for IFN-Gamma on Keratinocytes in Atopic Dermatitis Acute Skin Lesions

Abstract

Background: Atopic dermatitis (AD) is an allergic skin disease mediated by antigen-specific IgE and an important role has been ascribed to CD4+ cells (Th cells). The objective of the study was to evaluate humoral and cellular immunological factors in the blood and the skin lesions of AD patients, and to analyze the presence of inflammatory cell-surface markers in blood and skin biopsies. Methods: The parameters for monitoring of 40 AD patients included results of prick test to inhalant allergens and epicutaneous (patch) test to contact allergens; values of total IgE, serum immunoglobulins (IgG, IgA, IgM) and different cell markers in the sera (CD3, CD4, CD8, CD20, CD21, CD23, HLA-DR). We also analyzed the presence of inflammatory cell-surface markers (CD3, CD4, CD8, CD20, CD20, CD1a, CD23, CD29, CD45Ro, IFNγ+ markers) in the biopsies of skin lesions from 10 AD patients and 5 healthy controls (HCs) by immunohistochemical analysis (method of avidin-biotin immunoperoxidase). Results: Beside increased total serum IgE and positive skin tests, a significantly higher percentage of CD23+ cells with lower percentage of CD21+ cells was revealed in peripheral blood of AD patients in comparison to HCs. A positive epidermal expression of the majority of markers of T cells (CD3+, CD4+, CD8+, CD29+, CD45Ro+, IFNγ+) and those of Langerhans’ cells (LCs) (CD1a, CD23+), without those of B cells (CD20+) were noted in AD patients, but no in the skin of HCs. Furthermore, significant difference was also found between the two groups for increased expression of CD3, CD4, CD8, CD29, CD45Ro, IFNγ+ markers (markers for IFNγ receptor) and higher intraepidermal CD23+ LCs and intradermal CD1a+ LCs in AD skin lesions. Conclusions:The obtained results suggest involvement of various humoral factors with increased production of IgE and cooperation between Th subsets and LCs, with higher production of related cytokines, and disturbed cellular immunity, including epidermal LCs with IgE receptors of high and low affinity in AD. The annotation of activated Th1 cells with increased producing of IFNγ in acute AD skin lesions is notable, and might lead to IFNγ binding to keratinocytes and consequently inflammatory skin changes in the disease.

Topical Superantigen Exposure Induces Epidermal Accumulation of CD8+ T Cells, a Mixed Th1/Th2-Type Dermatitis and Vigorous Production of IgE Antibodies in the Murine Model of Atopic Dermatitis

“…Limited earlier evidence exists for the involvement of CD8 ϩ T cells in protein-induced allergic inflammation. Previous reports have shown that few CD8 ϩ T cells are found in the epidermis of AD patients but not in the epidermis of healthy controls (26). Furthermore, Huang et al (27) reported recently that epicutaneous exposure to mite allergen induces allergic dermatitis and the infiltration of few CD8 ϩ T cells into the epidermis.…”

Atopic Dermatitis: an Update and Review of the Literature

“…There are activated Th1 cells with increased production of IFNγ in acute AD skin lesions binding to keratinocytes and, consequently, inflammatory skin changes in the disease (22). A relative imbalance between Th1 and Th2 subsets of CD4+ T cells producing cytokines are indicative of prominent immune disorders in AD (22).…”

“…There are activated Th1 cells with increased production of IFNγ in acute AD skin lesions binding to keratinocytes and, consequently, inflammatory skin changes in the disease (22). A relative imbalance between Th1 and Th2 subsets of CD4+ T cells producing cytokines are indicative of prominent immune disorders in AD (22). AD is product of an interaction between various susceptibility genes, host and environmental factors, infectious agents, defects in skin barrier function and immunological responses (27).…”

“…Finally, a genetic linkage was shown to contribute to immunologic abnormalities of AD pathogenesis (22).…”

Correlation between serum IL-16 and atopic dermatitis

“…Total serum IgE might influence allergic inflammation in different ways. For example, its binding to FcR I on the surface of mast cells and basophils results in immediate hypersensitivity, and in combination with B cell surface FcR II, it initiates T cell-mediated immune responses (Bandeira-Melo et al, 2002;Lugović et al, 2005). IL-16 performs both chemotactic and immunoregulatory functions in inflammation.…”