title: Skin-homing T cells in human cutaneous allergic inflammation.
abstract: The cutaneous lymphocyte-associated antigen (CLA) is a carbohydrate epitope present on memory/effector T cells that infiltrate inflamed skin. E-selectin is the ligand for CLA and is induced under inflammation on endothelial cells. CLA was originally postulated as a phenotype marker for skin-associated T cells. We studied the specific in vitro response to skin-associated allergens of CLA+ and CLA-CD45RO+ T cells in atopic dermatitis (AD) and contact dermatitis (CD), which represent two well-characterized T cell-mediated cutaneous allergic inflammations. Whereas CLA+ T cells from AD patients preferentially responded to house dust mite (HDM) and CLA+ T cells from nickel CD patients showed an increased response to nickel, CLA-T cells showed very little response in both cases. In contrast, tetanus toxoid, a systemically acting antigen, induced a proliferative response in both CLA+ and CLA- cells. Interestingly the response to HDM in patients with asthma +/- AD was preferentially found in the CLA- subset indicating the involvement of different homing receptors for mucosal tissues. Moreover, CLA+ T cells showed enhanced migration through activated human umbilical vein endothelial cell monolayers compared to CLA- T cells. The CLA binding to E-selectin is initially responsible for the extravasation that also involves VLA-4/VCAM-1 and LFA-1/ICAM-1 interactions. We have recently identified IL-8 as an endothelial cell-derived chemokine and the IL-8 receptor type B which control CLA+ T cell migration. Such a CLA-mediated migration would localize memory/effector T cells that respond to antigens and reach the body through inflamed skin. Our data support the existence of a regionalization of the immune system and in particular of the skin immune system. It may allow an efficient distribution of the immune defense to different sites of the body.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
authors.forename: L F
authors.initials: LF
authors.lastname: Santamaria Babi
authors.forename: M T
authors.initials: MT
authors.lastname: Perez Soler
authors.forename: C
authors.initials: C
authors.lastname: Hauser
authors.forename: K
authors.initials: K
authors.lastname: Blaser
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D019040:E-Selectin / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D008925:Mites / Q000276:immunology; D009532:Nickel / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex; C063419:CTAGE1 protein, human; D019040:E-Selectin; D000939:Epitopes; D016209:Interleukin-8; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009532:Nickel; D017493:Leukocyte Common Antigens