SKIN DISEASE-RELATED T-CELLS BIND TO ENDOTHELIAL SELECTINS - EXPRESSION OF CUTANEOUS LYMPHOCYTE ANTIGEN (CLA) PREDICTS E-SELECTIN BUT NOT P-SELECTIN BINDING

Cutaneous lymphocyte antigen (CLA), defined by the HECA-452 antibody, is a cell surface glycoprotein found on a subset of T cells in periphe ral blood that binds specifically to E-selectin. This marker is presen t on the majority of T cells at sites of cutaneous inflammation and im mune responses. Based upon such evidence, an association between T cel l CLA expression and skin homing has been proposed. To understand bett er this relationship,we asked whether putative disease-related, antige n-specific T cells expressed CLA. In this study, we employed T helper type 2 (TH2) T cell clones specific for house dust mite (Dermatophagoi des pteronyssinus) antigens. These cells were derived from challenged skin of an individual known to react positively to epicutaneous challe nge 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 specifica lly to recombinant E-selectin. The CLA molecule on these cells was ide ntified 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 si milar conditions from peripheral blood were CLA negative or low and bo und poorly to E-selectin. Surprisingly, both skin and blood clones bou nd comparably to P-selectin. This binding was independent of S-Le(x) o r CLA expression. We conclude that in sensitized individuals, antigen- specific T cells expressing high levels of CLA localize in skin prompt ly after epicutaneous challenge. This localization is likely to involv e the interaction of S-Le(x) determinants on the CLA molecule with E-s electin on the dermal microvasculature. We further conclude that T cel ls can interact with P-selectin on endothelium and that S-Le(x) does n ot appear to be necessary for this interaction.