In vivo evidence for close association of CLA expression and E-selectin binding by T cells in the inflamed skin

Abstract

Tissue selective migration of lymphocytes is tightly regulated by expression of particular homing receptors on lymphocytes that interact with organ-specific adhesion molecules on specialized endothelial cells [ [1] Butcher E.C. Picker L.J. Lymphocyte homing and homeostasis. Science. 1996; 272: 60-66 Crossref PubMed Scopus (2503) Google Scholar ]. The skin-homing memory T cells subset is characterized by the expression of cutaneous lymphocyte-associated antigen (CLA), a carbohydrate epitope displayed on P-selectin glycoprotein ligand-1 (PSGL-1), defined by reactivity with the mAb HECA-452 [ 2 Picker L.J. Michie S.A. Rott L.S. Butcher E.C. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990; 136: 1053-1068 PubMed Google Scholar , 3 Picker L.J. Kishimoto T.K. Smith C.W. Warnock R.A. Butcher E.C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991; 349: 796-799 Crossref PubMed Scopus (733) Google Scholar , 4 Berg E.L. Yoshino T. Rott L.S. Robinson M.K. Warnock R.A. Kishimoto T.K. et al. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med. 1991; 174: 1461-1466 Crossref PubMed Scopus (498) Google Scholar , 5 Fuhlbrigge R.C. Kieffer J.D. Armerding D. Kupper T.S. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells. Nature. 1997; 389: 978-981 Crossref PubMed Scopus (468) Google Scholar ]. There has been considerable evidence that CLA+ memory T cells abound in the normal and inflamed skin, but not in other sites [ 2 Picker L.J. Michie S.A. Rott L.S. Butcher E.C. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990; 136: 1053-1068 PubMed Google Scholar , 3 Picker L.J. Kishimoto T.K. Smith C.W. Warnock R.A. Butcher E.C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991; 349: 796-799 Crossref PubMed Scopus (733) Google Scholar ]; and that CLA serves as the major, if not exclusive, T cell ligand for the vascular adhesion molecule E-selectin, which is constitutively-expressed on dermal endothelial cells [ 3 Picker L.J. Kishimoto T.K. Smith C.W. Warnock R.A. Butcher E.C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991; 349: 796-799 Crossref PubMed Scopus (733) Google Scholar , 4 Berg E.L. Yoshino T. Rott L.S. Robinson M.K. Warnock R.A. Kishimoto T.K. et al. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med. 1991; 174: 1461-1466 Crossref PubMed Scopus (498) Google Scholar ]. Thus, it is thought that the CLA/E-selectin interaction is required for an efficient T cell localization in the skin, and thereby responsible, at least in part, for the skin-homing selectivity of the CLA+ T cells subset. However, there is no in vivo direct evidence of CLA-bearing T cells migrating into the skin via an interaction with E-selectin.