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

Figure 1.3 ‐ Important events in the history of the IL‐17 and TH17 cell field [adapted from
(Gaffen, 2009)]
The discovery of Foxp3 + iTregs and Th17 cells and their close relationship, as well as the
identification of molecules that affect more than one T cell subset, described above, has
shown that these subsets have more in common than distinctions and, therefore, have
revised researcher’s concepts of CD4 + T helper cell commitment to a specific phenotype
as an endpoint. The concept of plasticity in T helper cells was based on the observation
that T cells show great flexibility in their differentiation options both in vivo and in vitro
depending on the milieu. For example, IL‐17 and IFNγ double positive population was
identified within CD4 + CNS‐infiltrating MOG peptide 35‐55 specific T cells in the CNS of
actively induced EAE sick mice (Suryani and Sutton, 2007). In the context of Th17 and
Foxp3 + iTregs cells, TGFβ can orchestrate both T cell differentiation programs in a
concentration‐dependent manner (Zhou et al., 2008). Also, all‐trans retinoic acid (ATRA)
induces Foxp3 + cells and decreases the frequency of Th17 cells, mediated by the nuclear
retinoic acid receptor‐alpha (RARα) (Schambach et al., 2007). Finally, there are Th1 cells
which produce simultaneously with IFNγ the anti‐inflammatory cytokine IL‐10 in certain
conditions such as infections in order to regulate their inflammatory reactions and
minimize immunopathology (O'Garra and Vieira, 2007).
34