impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

14
mechanisms of action remain undefined (Batten 2006,
Kleinschek 2007). More recently, a functional antagonism
between Th17 and Foxp3 + Treg cells has been
reported (Bettelli 2006). Th17 seems to originate not
only as a consequence of the production of IL-23 by
DCs, but mainly because of the combined activity of
IL-6 and TGF-β. Since TGF-β is also involved in the
generation of Treg cells (Chen 2003, Walker 2003,
Vieira 2004, Allan 2005), the fact that IL-6 inhibits
their development suggests the existence of a dichotomy
in the generation of pathogenic Th17 cells that can
induce autoimmunity and that of Foxp3 + Treg cells that
inhibit autoimmunity. Intrestingly, both IL-4 and IFN-γ
inhibit the development of Th17 cells (Iwakura 2006)
(Figure 2), whereas it is still unclear whether Th17 cells
exert any inhibitory effect on the development of Th1
and Th2 cells. Likewise, the precise effects of Tregs on
Th17 cells are as yet unknown.
In conclusion, the development of a polarized Th cell
from a naïve T-cell is a complex process involving stimulation
of TLRs, and activation and maturation of DCs,
Fig. 2. The complexity of the effector and regulatory network
of the CD4 T-cells. The availability of IL-4 in the absence of
IL-12 or IFN-γ results in the preferential development of Th2
effector cells, whereas the production of IL-12 by DCs
favours the differentiation of antigen-activated naïve T cells
into Th1 effectors. Th1 and Th2 cells differentiation tends to
be mutually exclusive through the secretion of IFN-γ and IL-
4, respectively. If a combination of IL-23, IL-6 and TGF-β is
produced by DCs, then the Th17 development is favoured.
However, both Th2 and Th1 cells can inhibit Th17 cells
through their secretion of IL-4 and IFN-γ, respectively.
Interestingly, TGF-β is important also for the development of
Treg cells, but IL-6 is inhibitory on this T-cell subset. Dashed
arrows indicate inhibitory circuits.
G. Del Prete - The complexity of the CD4 T-cell response
which leads to TCR engagement and cytokine release
that triggers distinct signaling cascades. The phenotype
of the T-cell that is generated is influenced by the tissue
microenvironment, the dominant cytokines, costimulatory
molecules and the nature and dose of antigen presented.
In any case, it is becoming clear that the pathway
of both effector and regulatory activities is much
more complex and tightly regulated than so far
thought.
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