Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS).
The etiology of MS is not well understood, but it is believed that myelin-specific
CD4+ T cells play a central role in initiating and orchestrating CNS inflammation. In
this scenario, CD4+ T cells, activated in the periphery, infiltrate the CNS, where, by secreting cytokines
and chemokines, they start an inflammatory cascade. Given the central role of CD4+ T cells in CNS autoimmunity, they have been studied extensively, principally by using
experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the late
1980s, CD4+ T cells, based on their cytokine production, were divided into two helper lineages,
Th1 and Th2 cells. It was postulated that Th1 cells, which produce IFN-γ, mediate
inflammation of the CNS in MS/EAE, while Th2 cells, which produce IL-4, have a beneficial
effect in disease, because of their antagonistic effect on Th1 cells. The Th1/Th2
paradigm remained the prevailing view of MS/EAE pathogenesis until 2005, when a new
lineage, Th17, was discovered. In a relatively short period of time it became apparent
that Th17 cells, named after their hallmark cytokine, IL-17A, play a crucial role
in many inflammatory diseases, including EAE, and likely in MS as well. The Th17 paradigm
developed rapidly, initiating the debate of whether Th1 cells contribute to EAE/MS
pathogenesis at all, or if they might even have a protective role due to their antagonistic
effects on Th17 cells. Numerous findings support the view that Th17 cells play an
essential role in autoimmune CNS inflammation, perhaps mainly in the initial phases
of disease. Th1 cells likely contribute to pathogenesis, with their role possibly
more pronounced later in disease. Hence, the current view on the role of Th cells
in MS/EAE pathogenesis can be called the Th17/Th1 paradigm. It is certain that Th17
cells will continue to be the focus of intense investigation aimed at elucidating
the pathogenesis of CNS autoimmunity.
Abbreviations:
IL (interleukin), IFN (interferon), MOG (myelin oligodendrocyte glycoprotein), MS (multiple sclerosis), CNS (central nervous system), EAE (experimental allergic encephalomyelitis), APC (antigen presenting cells), MBP (myelin basic protein), TNF (tumor necrosis factor), GM-CSF (granulocyte macrophage colony-stimulating factor), NO (nitric oxide), WT (wild-type), Tregs (regulatory T cells)Keywords
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Article info
Publication history
Published online: April 10, 2013
Accepted:
March 4,
2013
Received in revised form:
February 19,
2013
Received:
November 20,
2012
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
