Functional characterization of skin-infiltrating lymphocytes in atopic dermatitis.
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-alpha) 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-alpha upon stimulation with mitogens but failed to secrete IFN-gamma. Io in combination with phorbol-ester induced the secretion of larger amounts of IL-4, GM-CSF, TNF-alpha and low amounts of IFN-gamma. The data indicate that SIL derived from AD lesions were defective in their capacity to secrete IFN-gamma 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.
Reinhold
U
U
Department of Dermatology, University of Bonn, Germany.
Kukel
S
S
Goeden
B
B
Neumann
U
U
Kreysel
H W
HW
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D019002:CD56 Antigen; D016827:CD8 Antigens / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; D007376:Interleukin-2; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate