Skin-homing T cells in human cutaneous allergic inflammation.
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.
Santamaria Babi
L F
LF
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
Perez Soler
M T
MT
Hauser
C
C
Blaser
K
K
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
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