Disease activity in multiple sclerosis correlates with T lymphocyte expression of the inhibitor of apoptosis proteins

Abstract

The pathogenesis of multiple sclerosis (MS) is thought to involve failure of programmed cell death (apoptosis) to eliminate potentially pathogenic, autoreactive T lymphocytes. This failure may be caused by multiple abnormalities of the cell death machinery. The inhibitors of apoptosis (IAP) proteins are central regulators of cell death that inhibit apoptosis induced by a variety of stimuli. In this study, we investigated the dynamics of cellular IAP-1, IAP-2, and X-linked IAP, in resting and mitogen stimulated T lymphocytes from MS patients and relevant controls. The expression of IAP proteins was significantly higher in mitogen stimulated T lymphocytes from patients with clinically active MS when compared to corresponding expressions from patients with stable MS or from other controls. Heightened expression of IAP proteins in patients with active MS correlated with clinical features of disease activity, and with T lymphocyte resistance to apoptosis. In contrast, cellular expression of the anti-apoptosis protein Bcl-2 did not differ between active and stable MS, and was relatively similar between MS patients and controls. These findings suggest that overexpression of IAP proteins in stimulated T lymphocytes is a feature of clinically active multiple sclerosis.