title: Skin disease-related T cells bind to endothelial selectins: expression of cutaneous lymphocyte antigen (CLA) predicts E-selectin but not P-selectin binding.
abstract: Cutaneous lymphocyte antigen (CLA), defined by the HECA-452 antibody, is a cell surface glycoprotein found on a subset of T cells in peripheral blood that binds specifically to E-selectin. This marker is present on the majority of T cells at sites of cutaneous inflammation and immune responses. Based upon such evidence, an association between T cell CLA expression and skin homing has been proposed. To understand better this relationship, we asked whether putative disease-related, antigen-specific T cells expressed CLA. In this study, we employed T helper type 2 (TH2) T cell clones specific for house dust mite (Dermatophagoides pteronyssinus) antigens. These cells were derived from challenged skin of an individual known to react positively to epicutaneous challenge with this agent. In this study, we show that these cloned T cells showed very high homogeneous expression of CLA (nearly 500-fold higher than T cell clones derived from peripheral blood) and bound specifically to recombinant E-selectin. The CLA molecule on these cells was identified not only by HECA-452, but also by CSLEX-1, indicating that it contained sialyl-Le(x) (S-Le(x)) determinants. T cells cloned under similar conditions from peripheral blood were CLA negative or low and bound poorly to E-selectin. Surprisingly, both skin and blood clones bound comparably to P-selectin. This binding was independent of S-Le(x) or CLA expression. We conclude that in sensitized individuals, antigen-specific T cells expressing high levels of CLA localize in skin promptly after epicutaneous challenge. This localization is likely to involve the interaction of S-Le(x) determinants on the CLA molecule with E-selectin on the dermal microvasculature. We further conclude that T cells can interest with P-selectin on endothelium and that S-Le(x) does not appear to be necessary for this interaction.
authors.affiliation: Division of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: H
authors.initials: H
authors.lastname: Rossiter
authors.forename: F
authors.initials: F
authors.lastname: van Reijsen
authors.forename: G C
authors.initials: GC
authors.lastname: Mudde
authors.forename: F
authors.initials: F
authors.lastname: Kalthoff
authors.forename: C A
authors.initials: CA
authors.lastname: Bruijnzeel-Koomen
authors.forename: L J
authors.initials: LJ
authors.lastname: Picker
authors.forename: T S
authors.initials: TS
authors.lastname: Kupper
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002999:Clone Cells; D003876:Dermatitis, Atopic / Q000276:immunology*; D019040:E-Selectin; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008925:Mites / Q000276:immunology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins