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

inflammatory cytokines and cellular debris after injury or necrosis. In vitro studies have
shown that microglia are able to secrete a panel of inflammatory cytokines and
chemokines such as IL‐6, macrophage inflammatory protein‐2 (MIP‐2), nitric oxide,
adhesion molecules, and neurotrophic factors in response to IL‐17. Additionally, these
cells can also be an innate source of IL‐17 in response to IL‐23 or IL‐1β, contributing
therefore to inflammation in autoimmune diseases such as MS (Kawanokuchi et al.,
2008).
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1.4 ‐ THE PARADIGMS OF HELPER T CELL SUBSETS: MORE COMPLEX
THAN INITIALLY THOUGHT
There are several subsets of effector helper CD4 + T cells. Depending on the
microenvironment and cytokines released by the APCs, a naïve T cell responds to
presentation of the cognate antigen, in the context of the major histocompatibility
complex (MHC) class II, by differentiating to different helper T cell subsets. In 1986,
helper T cells were classified for the first time into two subsets, type 1 helper T cells
(Th1) and type 2 helper T cells (Th2), based in their cytokine production (Mosmann et
al., 1986). Th1 cells produce high amounts of interferon gamma (IFNγ) whereas Th2
cells produce interleukin‐4 (IL‐4), IL‐5 and IL‐13. The Th1/Th2 paradigm associated these
T cell populations with specific immune responses. While Th1 cells are specialized in
macrophage activation and defense against intracellular pathogens, including viruses
and some bacteria such as mycobateria, Th2 cells, in contrast, are particularly
important for defense against large extracellular pathogens such as helminths, for the
induction of immunoglobulin E (IgE) by B cells, mast cells activation and eosinophils
mobilization. Allergic diseases are characterized mainly by a Th2 response, whilst
autoimmune diseases are driven by Th1 cells. However, this paradigm soon proved to
be too simplistic as many observations from clinical diseases could not be explained by
this simple categorization. More recently, several subsets of Tregs capable of
controlling effector T cells responses were described: the thymus derived nTregs, and
the iTregs, Tr1 and Th3 regulatory T cells derived from peripheral helper T cell
precursors. Furthermore, in 2005 Dan Cua and colleagues described a new pathogenic
CD4 + T cell population that is driven by IL‐23, produces IL‐17, IL‐17F, IL‐6, and tumor