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

CNS. Finally, it was found that transferred Th17 cells can convert to a Th1 phenotype in
the host, suggesting plasticity in the Th17 cell subset and emphasizing a pathogenic role
for Th1 cells.
Next, taking into account our data and earlier findings previous to the Th17 cell
discovery that demonstrated a cytotoxic capacity of auto‐antigenic T cells over
astrocytes, important CNS resident glial cells, we asked which of the CD4 + T cell subset
was cytotoxic to astrocytes. By establishing an in vitro co‐culture of myelin‐specific Th1
and Th17 cells with GFP positive‐astrocytes, it was possible to pursue cytotoxicity by
fluorescent time‐lapse microscopy. It was found that Th1 but not Th17 cells were
cytotoxic to astrocytes, further emphasizing the pathogenic role of Th1 cells.
Finally, in order to identify molecules that are differently regulated in Th1 and Th17
cells and to understand which different roles these cells might play in EAE, a
transcriptome analysis by microarrays of both populations was performed. We found
the nuclear receptor Rev‐Erbα to be expressed in Th17 but not in Th1 cells. A pathway
analysis revealed a relationship of Rev‐Erbα with RORα, an important transcription
factor for Th17 differentiation, but no definite role for this molecule in regulating Th17
differentiation could be established.
In conclusion, this thesis demonstrates, contrary to initial evidence, that both myelin‐
specific Th1 and Th17 CD4 + T cell subsets are able to induce pathogenicity in EAE,
though with different capabilities to mediate disease. Also, Th1 cells are true cytotoxic
effector cells destroying astrocytes, important neuronal buffer cells. A new gene was
also discovered, Rev‐Erbα, which is differently regulated by Th1 and Th17 cells. Though
no impact of Rev‐Erbα in Th17 differentiation could be determined, a possible role in
Th17 biology will need to be further addressed.
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