Functional characterization of skin-infiltrating lymphocytes in atopic dermatitis

Abstract

SUMMARY Skin-infiltrating 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 3H-thymidine incorporation assays, SIL showed proliferation in response to IL-2, IL-3, IL-4, ionomycin (Io)+ 12-o-tetradecanoyl-phorbol-13-acetate (TPA) and OKT3 + TPA. OKT4 with and without TPA did not induce proliferation. Tumour necrosis factor alpha (TNF-α) 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-α upon stimulation with mitogens but failed to secrete IFN-γ. Io in combination with phorbolester induced the secretion of larger amounts of IL-4, GM-CSF, TNF-α and low amounts of IFN-γ. The data indicate that SIL derived from AD lesions were defective in their capacity to secrete IFN-γ 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.