role of th1 and th17 cd4+ t cell subsets in the pathogenesis of ...

a monoclonal antibody was found to be beneficial in acute EAE (Hofstetter et al., 2005)
and blocking IL‐23 function with anti‐IL‐23p19‐specific antibodies in EAE sick mice
inhibited multiple inflammatory pathways functions such as serum levels of IL‐17 and
CNS expression of IFNγ and IL‐17 (Chen et al., 2006). Also, IL‐17 deficient mice exhibited
delayed EAE onset and adoptive transfer of IL‐17 deficient CD4+ T cells, which carried
an increased number of IFNγ‐producing cells, inefficiently were able to induce EAE in
recipient mice (Komiyama et al., 2006). IL‐27 is a cytokine that suppresses Th17 cells
and IL‐27R alpha‐deficient mice were also found to be hypersusceptible to EAE (Batten
et al., 2006). In the absence of TGFβ signaling, mice were found to be deficient in Th17
cells and resistant to EAE immunization (Veldhoen et al., 2006c). More recently, the
restriction of IL‐23 receptor deficiency to defined cell populations in vivo showed that
Th17 cells failed to down‐regulate IL‐2 and maintain IL‐17 production, associated with
less proliferation and capacity to migrate to certain tissues (McGeachy et al., 2009),
demonstrating the requirement of IL‐23 signaling in the development and function of
Th17 cells in autoimmunity.
The observations involving the Th17 rather the Th1 cells pathogenicity in EAE might
comes might be explained by some interesting studies. First, the study of the role of
pertussis toxin as an immune adjuvant in active EAE demonstrated that pertussis toxin
inhibits the development of Tregs and induces IL‐17‐producing CD4 cells (Chen et al.,
2007). Additionally, mycobacteria and zymosan, a cell wall component of
Saccharomyces cerevisiae, when emulsified with MOG and incomplete Freund’s
adjuvant for immunization potentiate Th17 cell differentiation (Veldhoen et al., 2006c).
Therefore, the active EAE model might be already pre‐conditioned to a Th17 response,
masking the true role of T cells responses in CNS autoimmunity.
Other studies suggested the involvement of cytokines and transcription factors
affecting both Th1 and Th17 populations, previously associated with only one T cell
subset. MOG‐specific T cells from IL23p19KO mice, found to be highly deficient not only
in the production of IL‐17A but also of IFNγ, induced EAE with delayed onset and much
lower severity when transferred to WT recipient mice, indicating a critical role of IL‐23
in development of encephalitogenic T cells, towards both Th1 and Th17 pathways
(Thakker et al., 2007). Notwithstanding, another work focused on the suppression of T‐
bet described an amelioration of EAE, not only by limiting the differentiation of auto‐
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