Translational mini-review series on Th17 cells: CD4 T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation.

CD4(+) T cells display considerable flexibility in their effector functions, allowing them to tackle most effectively the range of pathogenic infections with which we are challenged. The classical T helper (Th) 1 and Th2 subsets have been joined recently by the Th17 lineage. If not controlled, the potent effector functions (chiefly cytokine production) of which these different cells are capable can lead to (sometimes fatal) autoimmune and allergic inflammation. The primary cell population tasked with providing this control appears to be CD4(+) regulatory T (T(reg)) cells expressing the forkhead box P3 (FoxP3) transcription factor. Here we consider the comparative capacity of FoxP3(+) T(regs) to influence the polarization, expansion and effector function of Th1, Th2 and Th17 cells in vitro and in vivo as well as in relation to human disease. This remains a particularly challenging series of interactions to understand, especially given our evolving understanding of T(reg) and T effector interrelationships, as well as recent insights into functional plasticity that cast doubt upon the wisdom of a strict categorization of T effector cells based on cytokine production.