Experimental autoimmune encephalomyelitis: Cytokines, effector t cells, and antigen-presenting cells in a prototypical th1-mediated autoimmune disease

Abstract

Experimental autoimmune encephalomyelitis (EAE) is widely depicted as the prototypical CD4+ Th1-mediated autoimmune disease. Microglia and perivascular macrophages are believed to act as antigen-presenting cells during the effector phase of EAE. In this article, recent data that challenge these conceptions are reviewed. Several recent studies have shown that myelin-reactive CD8+ T cells can mediate inflammatory demyelination. Furthermore, dendritic-like cells have been detected in EAE lesions and implicated in encephalitogenic T-cell activation. Although Th1 polarizing monokines, such as interleukin-12 (IL-12) and possibly IL-23, are critical for the manifestation of EAE, individual Th1 effector cytokines were found to be dispensible.

Neuroprotection without Immunomodulation Is Not Sufficient to Reduce First Relapse Severity in Experimental Autoimmune Encephalomyelitis

“…We observed increased amounts of TNF-␣ , IL-12 and IFN-␥ in the CNS of control animals treated with IFA+PBS only. This is probably due to an adjuvant-induced increase in the blood-brain barrier permeability, as also shown by others [50] , and it might explain why EAE has been considered a prototypic T H 1-mediated disease [41,51] .…”

“…3 ), which challenges the theory that the T H 1 response is detrimental in MS/EAE. The essential aspect concerning cytokines seems to be timing in relation to disease state [41,42] . Thus, TNF-␣ and IFN-␥ might be detrimental in inducing resident CNS cell death during the initial stages of the disease, but later these cytokines may play a beneficial role in inducing remyelination and immune cell death, as shown in other studies [37,[43][44][45][46][47] .…”

Modulatory effect of celastrol on Th1/Th2 cytokines profile, TLR2 and CD3+ T-lymphocyte expression in a relapsing–remitting model of multiple sclerosis in rats

“…In this context, the EAE model in this work exhibited a T cell-mediated immune response in favor to Th1 pattern over Th2 pattern reflected as an imbalance in their associated cytokines where the pro-inflammatory TNF-α was significantly increased without change in the anti-inflammatory IL-10. Previous studies reported that Th2-related cytokines including IL-10 have been associated with inflammation reduction and improvement of symptoms in MS patients, while Th1 cytokines such as TNF-α have been shown to increase inflammation with subsequent disease progression and worsening of symptoms (Sharief and Hentges, 1991;Segal, 2003;Miller et al, 2004;Imitola et al, 2005). TNF-α mediates inflammatory reaction by altering the blood brain barrier, influences lymphocyte behavior, and induces tissue damage with astrogliosis and destruction of oligodendrocytes (Issazadeh et al, 1995;Montgomery and Bowers, 2012).…”

Transplanting of Mesenchymal Stem Cells May Affect Proliferation and Function of CD4+T Cells in Experimental Autoimmune Encephalomyelitis

“…The demyelination of the CNS was concerned with the overactivity of effector T cells, infiltration of inflammatory cells in the CNS, increased production of proinflammatory cytokines, and inflammatory molecules. 5,6 Cytokines such as…”