The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1.

Abstract

SummaryA skin-associated population of memory T lymphocytes, defined by expression of the cutaneous lymphocyte antigen (CLA), binds selectively and avidly to the vascular lectin endothelial cellleukocyte adhesion molecule 1 (ELAM-1), an interaction that may be involved in targeting of CLA + T cells to cutaneous sites of chronic inflammation. Here we present evidence that CLA itself is the (or a) lymphocyte homing receptor for ELAM-1. Antigen isolated with anti-CLA monoclonal antibody HECA-452 from human tonsillar lysates avidly binds ELAM-1 transfected mouse cells. Anti-CLA antibody blocks T lymphocyte binding to ELAM-1 transfectants. HECA-452 and ELAM-1 binding to lymphocytes or to isolated tonsillar HECA-452 antigen is abrogated by neuraminidase treatment implying a prominent role for sialic acid in CLA structure and function. The dominant form of CLA on T cells is immunologically distinct from the major neutrophil ELAM-1 ligand, the sialyl Lewis x (sLe ~) antigen (NeuAcc~2-3GalB1-4[Fuccxl-3]GlcNAc), which is absent, weakly expressed, or masked on T ceUs. However, neuraminidase treatment of CLA + T cells, but not of CLA-T cells, reveals Lewis x (CD15) structures. In combination with the known requirement for terminal NeuAcoe2-3Gal and fucose residues attached to N-acetylglucosamine for ELAM-1 and HECA-452 binding, this finding suggests that CLA may comprise an additionally sialylated or otherwise modified form of sLe x. The identification of a lymphocyte homing receptor for skin may permit novel approaches to the diagnosis and therapy of cutaneous and inflammatory disorders.

Fucosyltransferase VII-Deficient Mice with Defective E-, P-, and L-Selectin Ligands Show Impaired CD4+ and CD8+ T Cell Migration into the Skin, but Normal Extravasation into Visceral Organs

“…CLA is expressed by neutrophils, monocyte subsets, a small fraction of leukocytes in lymph nodes, and endothelium at sites of chronic inflammation. Most notably, CLA has been characterized as a specialized carbohydrated form of PSGL-1 (42), which is specifically expressed on skin-homing T cells (42)(43)(44)(45). PSGL-1 displays sialyl Lewis x-like carbohydrate determinants, which require fucosylation with FucTVII (46), and has recently been identified as the predominant ligand for L-selectin expressed on vascular endothelium (41).…”

Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

“…The frequent expression of the chemokine (C-C motif) receptor 4 (CCR4) on the surface of tumor cells may in part explain skin involvement [45,46]. Other factors such as expression of cutaneous lymphocyte antigen (CLA) [47,48], expression of lymphocyte chemoattractant chemokine, stromal cell-derived factor/pre-B-cell growth-stimulating factor (SDF-1/PBSF) [45], as well as inflammatory responses may lead to chemotaxis of infected lymphocytes [49] and contribute to skin infiltration by ATL cells. Virus-infected cells can remain in the skin for several months or years before their dissemination to the peripheral blood and organs.…”

Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis

“…This inefficient trafficking of cultured TILs is in contrast to the efficient removal of relevant T cells from the circulation that occurs in normal homing (Fisher and Ottaway, 1990;Picker and Butcher, 1992 (Picker et al, 1990a). CLA, a heavily glycosylated carbohydrate epitope on cell surface glycoproteins, is expressed at low levels on less than 20% of PBT (Berg et al, 1991;Picker et al, 1993a). In vivo, CLA is expressed on cutaneous lymphomas (Picker et al, 1990a) and on 85% of T cells at sites of skin inflammation (Picker et al, 1990a).…”

“…Selectivity is introduced by the existence of tissue-specific adhesion molecules on T cells that direct migration to particular organs (Butcher and Picker, 1996). This is particularly relevant for the skin, in which T cells activated in peripheral lymph nodes express the cutaneous lymphocyte antigen (CLA), which allows them to bind to E-selectin expressed on dermal endothelium, thereby promoting skin tropism (Picker et al, 1990a(Picker et al, , 1993aBerg et al, 1991). There is recent evidence that tumour-/tissue-specific 1422 OH Adams et al adhesion pathways can regulate the adhesion of TILs to tumour endothelium, suggesting that tissue-specific factors may regulate TIL recruitment to tumour in a manner analogous to that seen with normal T-cell recirculation (Salmi et al, 1992;Salmi et al, 1995;.…”