More MS news articles for August 2002

Reduced expression of the inhibitor of apoptosis proteins in T cells from patients with multiple sclerosis following interferon- therapy

Journal of Neuroimmunology, Vol. 129 (1-2) (2002) pp. 224-231
M.K. Sharief a, M.A. Noori a and Y. Zoukos b
a Department of Neuroimmunology, Guy's, King's and St Thomas' School of Medicine, Hodgkin Building, Guy's Hospital, London SE1 1UL, England, UK
b Department of Neurology, King's College Hospital, London, England, UK

Treatment with interferon-b reduces clinical exacerbations in multiple sclerosis (MS) through several immunomodulatory mechanisms that involve the augmentation of programmed cell death (apoptosis) of peripheral T lymphocytes.

The recently identified family of inhibitor of apoptosis (IAP) proteins is a potent regulator of cell death.

The expression of IAP-1, IAP-2, and X-linked IAP (XIAP) is upregulated in mitogen stimulated T lymphocytes from MS patients, and this expression correlates with MS disease activity.

In this study, we sought to evaluate the effect of interferon-b on cellular expression of IAP proteins and other apoptosis regulatory molecules.

In a prospective study, we evaluated the expression of IAP proteins, the anti-apoptosis Bcl-2 protein, and the death receptor Fas in in vitro stimulated T lymphocytes from MS patients, before and serially after treatment with interferon-b.

We also investigated the long-term effects of interferon-b on cellular expression of these proteins and T lymphocyte apoptosis in a cross-sectional study of MS patients receiving drug therapy for a mean of 4.8 years.

Treatment with interferon-b reduced the expression of IAP-1, IAP-2 and XIAP in stimulated T lymphocytes.

This reduced expression correlated with increased T cell susceptibility to apoptosis and with clinical response to treatment.

In contrast, interferon-b therapy did not alter cellular expression of Bcl-2 protein or the death receptor Fas.

This downregulatory effect of interferon-b on cellular expression of IAP proteins was maintained following long-term therapy.

Our findings suggest that interferon-b therapy exerts a regulatory effect on peripheral T lymphocytes through an anti-apoptosis mechanism that involves the downregulation of cellular IAP proteins expression.

© 2002 Elsevier Science B.V.