Journal
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER
Volume 192, Issue 4, Pages 179-193Publisher
ELSEVIER GMBH
DOI: 10.1016/j.aanat.2010.06.006
Keywords
CD4/T(H)1 paradigm; Heterogeneity; EAE; MS
Categories
Ask authors/readers for more resources
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) have long been regarded as primarily T helper cell type 1-mediated diseases However, recent evidence suggests that T-H 17 cells, a mostly unexplored subset of T helper cells, may be even more pathogenic than cells In the EAE model, this cell type is crucial for the recruitment of leukocytes into the CNS and for triggering parenchymal inflammation In humans, T(H)17 cells are found in acutely active and on the borders of chronically active lesions. Overall, CD4(+) T cells only recognize antigens presented on MHC class II complexes, and these are seldom found in the CNS MHC class I, in contrast, can be Induced on neurons and myelin This also makes CD8(+) T cells promising candidates as effector cell types. Indeed, CD8(+) T cells outnumber CD4(+) T cells in the lesions of MS patients, and can Induce axonal pathology. New data on B cells have likewise stimulated unconventional paths of reasoning about the disease. B cells can contribute to the pathogenesis by secreting autoantibodies and presenting antigens to T cells. By the formation of ectopic B cell aggregates in the CNS. B cell differentiation and response can take place remote from the periphery, thus autonomously fueling pathology. In addition, cells of the innate Immune system including macrophages, dendritic cells and mast cells are present in the inflamed CNS On the one hand, these cells can recognize pathogen-associated molecular patterns via Toll-like receptors (TLRs), generating proinflammatory signals that trigger adaptive immune responses On the other hand, these cells support the autoimmune process by the secretion of effector molecules such as nitric oxide (NO) Apart from a solely pathogenic autoimmune role, regulatory T cells, NK cells and NKT cells can suppress autoreactive cells In this paper, we review data on how a complex network of immune mechanisms is involved in the pathogenesis of MS and EAE. We also critically reevaluate the traditional CD4/T(H)1 paradigm. (C) 2010 Elsevier GmbH All rights reserved
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available