Upregulation of TRAIL expression on human T lymphocytes by interferon b and glatiramer acetate

Abstract

We measured the in vivo and in vitro effects of interferon (IFN)b and glatiramer acetate (GA) on the expression of the regulatory molecule, tumor necrosis factor related apoptosis inducing ligand (TRAIL), in patients with multiple sclerosis (MS). We confirmed the prior observation that TRAIL is enhanced on anti-CD3 activated T cells by the in vitro addition of IFNβ. T cells from IFNβ-treated patients stimulated with anti-CD3 only, had higher levels of TRAIL than untreated patients, suggesting that in vivo IFNβ exposure has an effect on TRAIL expression in association with T cell activation. In vitro IFNβ-induced TRAIL upregulation on anti-CD3 or phytohemagglutinin-activated T cells was comparable for IFNβ-treated and non-treated MS patients and controls, indicating that IFN receptors were neither saturated nor down-regulated by current IFNβ therapy. Although GAin vivo orin vitro did not induce TRAIL, the IFNβ-GA combination in vitro enhanced TRAIL expression to higher levels than IFNβ alone on CD4+ T cells obtained from MS patients, regardless of GA treatment status, and healthy donors, and on GA reactive T cell lines derived from GA-treated patients or controls. Whether any observed therapeutic effects of GA/IFNβ combination therapy will correlate with TRAIL expression and function remains to be determined.

Keywords

flow cytometry glatiramer acetate interferon type I multiple sclerosis TRAIL T lymphocytes

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