Association between parasite infection and immune responses in multiple sclerosis
Article first published online: 17 JAN 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 61, Issue 2, pages 97–108, February 2007
How to Cite
Correale, J. and Farez, M. (2007), Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol., 61: 97–108. doi: 10.1002/ana.21067
- Issue published online: 21 FEB 2007
- Article first published online: 17 JAN 2007
- Manuscript Accepted: 28 NOV 2006
- Manuscript Revised: 21 NOV 2006
- Manuscript Received: 24 JUL 2006
To assess whether parasite infection is correlated with a reduced number of exacerbations and altered immune reactivity in multiple sclerosis (MS).
A prospective, double-cohort study was performed to assess the clinical course and radiological findings in 12 MS patients presenting associated eosinophilia. All patients presented parasitic infections with positive stool specimens. In all parasite-infected MS patients, the eosinophilia was not present during the 2 previous years. Eosinophil counts were monitored at 3- to 6-month intervals. When counts became elevated, patients were enrolled in the study. Interleukin (IL)-4, IL-10, IL-12, transforming growth factor (TGF)-β, and interferon-γ production by myelin basic protein–specific peripheral blood mononuclear cells were studied using enzyme-linked immunospot (ELISPOT). FoxP3 and Smad7 expression were studied by reverse-transcriptase polymerase chain reaction.
During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients. Furthermore, myelin basic protein–specific responses in peripheral blood showed a significant increase in IL-10 and TGF-β and a decrease in IL-12 and interferon-γ–secreting cells in infected MS patients compared with noninfected patients. Myelin basic protein–specific T cells cloned from infected subjects were characterized by the absence of IL-2 and IL-4 production, but high IL-10 and/or TGF-β secretion, showing a cytokine profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of CD4+CD25+ FoxP3+ T cells was substantially increased in infected patients compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not detected in T cells from infected MS patients secreting TGF-β.
Increased production of IL-10 and TGF-β, together with induction of CD25+CD4+ FoxP3+ T cells, suggests that regulatory T cells induced during parasite infections can alter the course of MS. Ann Neurol 2007