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Access through your institution Buy or subscribe Writing in _Nature Immunology_ in June 2006, Robert Coffman — who together with Timothy Mossman was one of the founding fathers of the
TH1–TH2-cell hypothesis — expressed his expectation that ultimately “the understanding of immune regulation will exceed the ability of the original TH1–TH2 hypothesis to adequately organize
and explain it.” In April 1986 in the _Journal of Immunology_, Coffman and Mossman were the first to show at a clonal level that CD4+ T cells could be divided into two subsets on the basis
of cytokine production. However, they cautioned that their research “raises the question of the total diversity of T cell phenotypes. [...] it is quite possible that other T cell types exist
_in vivo_.” Indeed, since 2006, we have recognized TH17 cells as a third T-cell lineage, and T follicular helper cells might also be a distinct T-cell subset. Two studies in the December
2008 issue of _Nature Immunology_ show that TH2 cells can be reprogrammed by TGFβ to become a new functional subset that produces IL-9 and IL-10. Together, these studies support the idea
that CD4+ T cells have more functional plasticity than previously appreciated, an idea that is explored in the accompanying Poster, produced with support from UCB. This is a preview of
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CITE THIS ARTICLE From the editors. _Nat Rev Immunol_ 9, 71 (2009). https://doi.org/10.1038/nri2492 Download citation * Issue Date: February 2009 * DOI: https://doi.org/10.1038/nri2492 SHARE
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