Distinctive features of classic and non-classic (Th17-derived) human Th1 cells

T helper 17 (Th17) lymphocytes represent a third arm of the CD4(+) T-cell effector responses, in addition to Th1 and Th2 cells. Th17 cells have been found to exhibit high plasticity because they rapidly shift into the Th1 phenotype in inflammatory sites. In humans, Th1 cells derived from Th17 cells express CD161, whereas classic Th1 cells do not; these Th17-derived Th1 cells have been termed "non-classic Th1 cells. In this study, we examined similarities and differences between classic and non-classic human Th1 cells by assessing a panel of T-cell clones, as well as CD161(+) or CD161(-) CD4(+) T cells derived ex vivo from the circulation of healthy subjects or the synovial fluid of patients with juvenile idiopathic arthritis. The results show that non-classic Th1 cells can be identified based on CD161 expression, as well as the consistent expression of retinoic acid orphan receptor C, IL-17 receptor E, CCR6 and IL-4-induced gene 1, which are all virtually absent in classic Th1 cells. The possibility to distinguish these two cell subsets by using such a panel of markers may allow the opportunity to better establish the respective pathogenic roles of classic and non-classic (Th17-derived) Th1 cells in different chronic inflammatory disorders.