This study provides very interesting data, originally generated by microarray-based transcriptome studies comparing Th1, Th2 and Th17 clones, from which CD161 came out as a new surface marker to identify Th17 cells in vivo. Thus, the co-expression of CD161 and CXCR6 seems to be a valuable marker combination to differentiate between CD4 T cell subsets. The definite and simple detection and subsequent isolation of human Th17 cells by standard flow cytometry methods are a great challenge for monitoring Th17-mediated immune responses and for characterizing their immunopathological role in autoimmunity and chronic inflammation in vivo and in vitro. The results here also clearly indicate that human Th17 cells exclusively originate from NKT-like naive CD4-/CD161-double-positive precursor cells which were only detectable in umbilical cord blood and not in peripheral blood from adults. Only CD161-positive, naive CD4 cord blood cells co-expressed constitutively RORgammat, IL-23R and CCR6 and were able to differentiate in vitro into Th17 cells under the influence of IL-1beta, IL-23 and T-cell receptor (TCR) engagement. Unfortunately, this study could not provide any indication of whether CD161-positive and CD161-negative naive CD4 lymphocytes represent separate lineages or whether one subpopulation originates from the other. Furthermore, it would be interesting to explore the functional consequence of CD161 expression in Th17 precursor cells in comparison to CD161-negative cells. However, the encouraging data presented here make it reasonable to assume that new findings in the human Th17 research field won't be long in coming.