Functional characterization of skin-infiltrating lymphocytes in atopic dermatitis

Abstract

SUMMARYSkin-infiltralitig lymphocytes (SIL) were isolated from skin biopsies of patients with hyperimmunoglobulin E (IgE) atopic dermatitis (AD) and expanded in vitro in the presence of IL-2 in combination with IL-4. Phenotypic analysis of skin-derived cells revealed the predominance of CD4+ T helper/inducer phenotype in SIL populations. In ^H-thymidine incorporation assays, SIL showed proliferation in response to lL-2, IL-3, IL-4, ionomycin (Io)+ll-o-tetradecanoyl-phorbol-Hacetate (TPA) and OKT3 -\-TPA. OKT4 with and without TPA did not induce proliferation. Tumour necrosis factor alpha (TNF-a) did not block proliferative responses of SIL to IL-2 and IL-4. Cultured SIL showed no cytotoxic activity against K562 and Jurkat target cells. Expanded skin-derived T cells were tested for their capacity to secrete several cytokines in vitro. SIL secreted significant amounts of IL-4, GM-CSF and TNF-a upon stimulation with mitogens but failed to secrete IFN-y. Io in combination with phorbolester induced the secretion of larger amounts of IL-4, GM-CSF, TNF-a and low amounts of I FN-y. The data indicate that SIL derived from AD lesions were defective in their capacity to secrete IFN-y but were enriched in T cells capable of producing IL-4 upon stimulation. The results support the possibility of a predominant 'TH2-like' cell-mediated immune response in lesional skin of AD patients.

Immunohistochemical Characterization of the Pancreatic Cellular Infiltrate in Normal Pancreas, Chronic Pancreatitis and Pancreatic Carcinoma

“…The mechanism and significance of local imbalance in leukocyte subsets in diseases are not well understood. It is generally accepted that autoimmune reactions were associated with the accumulation of CD4+ T cells as it has been demonstrated in rheumatoid arthritis [14,15], primary biliary cirrhosis [16], and in atopic dermatitis [17].…”

Cutaneous CD30+ Cells in Children with Atopic Dermatitis

“…On serial sections, the expression of CD30 antigen was predominantly detected on CD4+ T cells. In vitro cloning studies have found that most CD4+ T cells in the lesional skin of patients with AD express a Th2-like phenotype [5, 6, 7]. CD30 expression in skin-infiltrating T cell clones of AD patients has been found to be strongly correlated with the production of IL-4 and IL-5, but to be inversely related to IFN-γ [18].…”

“…In vitro studies have demonstrated that cytokines derived from Th2 cells, such as interleukin-4 (IL-4), IL-10 and IL-13, are involved in IgE production and in the development of immediate hypersensitivity reactions [4]. In AD, a large proportion of skin-infiltrating Th cells express a Th2-like phenotype [5, 6, 7]. The production of Th2-type cytokines is associated with membrane expression of the glycoprotein CD30 in both CD4+ and CD8+ cell clones [8], and CD30 expression is regulated by IL-4 [9].…”

Soluble CD30 and Cyclosporine in Severe Atopic Dermatitis

“…In vitro cloning studies have provided valuable information about the functional nature of skin-infiltrating CD4+ T cells in patients with AD, as the majority of these cells express a Th2-like phenotype and some of them are specific for common environmental allergens [6, 7]. Moreover, spontaneous release of Th2-type cytokines has been demonstrated in supernatants of both peripheral blood lymphocytes and skin biopsies of AD patients [8]even if other reports suggest a potential role for IFN-γ in AD, as IFN-γ mRNA expression and not IL-4 is increased in chronic AD lesional skin [9, 10].…”