The functional plasticity of T cell subsets

In 1986, Robert Coffman and Timothy Mossman first described the division of CD4(+) T cells into functional subsets, termed T helper 1 (T(H)1) and T(H)2, based on cytokine production, and in doing so unwittingly opened a Pandora's box of complexity and controversy. Although the mechanisms that regulate T(H)1 and T(H)2 cells are now well known, recent descriptions of other CD4(+) T cell subsets-such as regulatory T cells, T follicular helper cells, T(H)17, T(H)22 and most recently T(H)9 and T(H)22 cells-have questioned how we think of T cell subsets and what commitment to a functional T cell subset means. Here, Nature Reviews Immunology asks four leaders in the field their thoughts on the functional plasticity of T cell subsets.