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Skin-homing T cells in human cutaneous allergic inflammation

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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 skinassociated 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.

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Santamaria Babi, L.F., Perez Soler, M.T., Hauser, C. et al. Skin-homing T cells in human cutaneous allergic inflammation. Immunol Res 14, 317–324 (1995). https://doi.org/10.1007/BF02935627

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