Interleukin 17–producing CD4+ Effector T Cells Develop Via a Lineage Distinct from the T Helper Type 1 and 2 Lineages

CD4 + T cells producing interleukin 17 (IL-17) are associated with autoimmunity, although the precise mechanisms that control their development are undefined. Here we present data that challenge the idea of a shared developmental pathway with T helper type 1 (T H 1) or T H 2 lineages and instead favor the idea of a distinct effector lineage we call 'T H -17'. The development of T H -17 cells from naive precursor cells was potently inhibited by interferon-γ (IFN-γ) and IL-4, whereas committed T H -17 cells were resistant to suppression by T H 1 or T H 2 cytokines. In the absence of IFN-γ and IL-4, IL-23 induced naive precursor cells to differentiate into T H -17 cells independently of the transcription factors STAT1, T-bet, STAT4 and STAT6. These findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic T H -17 effector cells that can exacerbate autoimmunity.