Activation-independent binding of human memory T cells to adhesion molecule ELAM-1

Abstract

The induction of an ensemble of adhesion molecules on endothelial cells by inflammatory cytokines is likely to be crucial to the differential migration of T-lymphocyte subsets into inflammatory sites. Two molecular pathways involving the VLA-4 and LFA-1 integrins are known to mediate T-cell adhesion to activated endothelium. Here we show that a third pathway involving the rapidly inducible endothelial cell-surface adhesion molecule ELAM-1 contributes to the binding of resting CD4+ T cells to IL-1-induced human endothelial cells. All three pathways contribute to the greater adhesion to endothelium of memory T cells than naive T cells. There are two unique features of T-cell adhesion to purified ELAM-1: first, ELAM-1 exclusively mediates adhesion of memory T cells; second, memory T-cell binding to ELAM-1 is independent of acute activation events that regulate integrin-mediated adhesion. Thus, ELAM-1 may be of primary importance in the initial attachment of memory T cells to inflamed endothelium in vivo and to the preferential migration of memory T cells into tissue and inflammatory sites.

Regulation of adhesion molecule expression by human synovial microvascular endothelial cells in vitro

“…E-selectin is important in tethering polymorphonuclear leukocytes and memory T lymphocytes to the endothelium (29,30). In contrast, ICAM-1 plays a role in both basal leukocyte adhesion and transendothelial migration (3 1).…”

Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis X, a selectin ligand expressed on a subset of skin-homing helper memory T cells

“…The sialyl 6-sulfo Le x determinant was significantly expressed on helper memory T and NK cells among human peripheral lymphocytes. These nonactivated helper memory T cells were known to adhere to E-selectin, 6 but the selectin ligand on this T-cell subset had been poorly detected by anti-sialyl Le x antibodies such as CSLEX-1. Only distinct anti-sialyl Le x antibodies, such as HECA-452 and 2F3, effectively detected the ligand.…”

“…6,7 The HECA-452 antibody is reactive to sialyl 6-sulfo Le x and nonsulfated conventional sialyl Le x , but the determinant detected by this antibody on the skinhoming helper memory T cells in normal peripheral blood must be mainly sialyl 6-sulfo Le x because nonsulfated conventional sialyl Le x is hardly detectable on these cells. The advantage of HECA-452 in studies of various skin diseases to date is that it has long been an unrivaled reagent in detecting sialyl 6-sulfo Le x specifically expressed on skin-homing helper memory T cells.…”

“…5 The HECA-452 antibody defining CLA was shown to recognize the sialyl Lewis X (Le x ) determinant, which is known as a typical carbohydrate ligand for selectins, the cell adhesion molecules that are involved in leukocyte-endothelial and leukocyte-leukocyte interactions. [6][7][8][9][10] An antibody, 2F3, one of the antibodies raised against chemically synthesized sialyl Le x determinant, was also shown to detect a similar helper memory T-cell population as HECA-452 and has been used to characterize skin infiltration of adult T-cell leukemia cells. [11][12][13][14] The puzzling phenomenon, however, has been that some anti-sialyl Le x antibodies, such as CSLEX-1, fail to effectively detect the skin-homing helper memory T-cell subset, whereas only a few anti-sialyl Le x antibodies, such as HECA-452 and 2F3, define the subset.…”

The effect of herpesvirus infection on the expression of cell adhesion molecules on cultured human dermal microvascular endothelial cells

“…The binding of T-lymphocytes to endothelial cells is governed by the expression of cell adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) [7], vascular cell adhesion molecule 1 (VCAM-1) [8], or E-selectin [9].…”