Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

Abstract

SUMMARYThis study investigated the adherent properties and adhesion molecule expression of blood mononuclear cells (MNC) from a total of 84 patients with multiple sclerosis (MS). The MNC from MS patients were significantly more adherent than cells from normal healthy subjects to endothelial monolayers pretreated with 0 . 01 U/ml TNF-® (103% increase; P 0 . 002), 0 . 1 U/ml TNF-® (80% increase; P < 0 . 01) and 1 . 0 U/ml TNF-® (41% increase; P < 0 . 02), and to endothelium pretreated with 10 U/ml IL-1¯(44% increase; P < 0 . 05) and 100 U/ml interferon-gamma (IFN-°) (100% increase; P < 0 . 05). This augmented adhesion was a property of the lymphocytes, in particular CD4 + cells, and was inversely related to the time of onset of clinical relapse. The percentage of lymphocytes bearing the adhesion molecules CD49d, CD29 and CD62L was increased in MS blood, but the level of CD29 and CD62L expression was reduced. We infer that circulating lymphocytes in MS are predisposed to cross endothelial barriers at sites where inflammation has already commenced.

Immunological effects of in vivo interferon-β 1b treatment in ten patients with multiple sclerosis: a 1-year follow-up

“…These data are in agreement with those reported by Tsukada et al [22] and Vora et al [23], who found enhanced adhesion to cerebral endothelium only in patients in relapse and in chronic-progressive MS patients. The long-lasting reduction in adhesion phenomena between PBMNCs from IFN-β 1b -treated MS patients and endothelium, however, speaks in favor of a possible inhibiting effect of in vivo IFN-β 1b on the formation of perivascular infiltrates, at least partly mediated by modulation of adhesion molecules.…”

Differential expression ofβ1 andβ2 integrins and L-selectin on CD4+ and CD8+ T lymphocytes in human blood: comparative analysis between isolated cells, whole blood samples and cryopreserved preparations

“…Following cell activation CD62L is cleaved from the surface [21,22] and this effect may have contributed to its decreased distribution and low level of expression on CD4 + and CD8 + T lymphocytes during the thawing of cryopreserved cells. Additional studies by our group show that cryopreservation does not alter the adhesive properties of T lymphocytes for cultured endothelium in a static adherence assay [23] and for blood vessel walls exposed in tissue sections of normal brain. However, the same caveat is unlikely to apply to the ‘tethering’ of T lymphocytes to endothelial cells and to recognition of addressins on high endothelial venules, since each of these events is dependent upon CD62L expression.…”