Upregulation of the inhibitor of apoptosis proteins in activated T lymphocytes from patients with multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) may 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. In this study, we investigated the expression of the inhibitors of apoptosis (IAP) proteins, cellular IAP-1, IAP-2, and X-linked IAP (XIAP), in T lymphocytes from patients with active relapsing-remitting MS and appropriate controls. The expression of IAP proteins was significantly higher in mitogen-stimulated intrathecal and peripheral T lymphocytes from MS patients when compared to corresponding expressions from inflammatory and non-inflammatory neurologic controls, and healthy individuals. IAP proteins were also expressed in resting (unstimulated) T lymphocytes predominantly from MS patients. The heightened expression of IAP proteins in MS patients correlated with T lymphocyte resistance to apoptosis, and was independent of cellular expression of the death receptor protein Fas. In contrast, cellular expression of the anti-apoptosis protein Bcl-2 was relatively similar between MS patients and the control groups. These findings suggest that over-expression of IAP proteins in mitogen-stimulated T lymphocytes is a feature of multiple sclerosis.