The selective expression of chemokine receptors, a feature that allows different effector-cell subsets to home to different sites, can be used to distinguish subsets of memory T cells. So, Acosta-Rodriguez et al. sorted T cells from human peripheral blood according to their expression of CCR7 (CC-chemokine receptor 7), CCR6, CCR4 and CXCR3 (CXC-chemokine receptor 3) and assayed for cytokine production in the ensuing memory CD4+ T-cell subsets. TH17 cells were detected in both CCR7+ (central memory) and CCR7− (effector memory) CD4+ T-cell subsets. As expected, interferon-γ (IFNγ)-producing TH1 cells were enriched in the CXCR3+ population. Surprisingly, however, the expression of CCR6, which mediates homing to the skin and mucosal tissues, precisely identified all TH17 cells. But the CCR6+ subset also contained TH1 cells and a subset of cells that produced both IL-17 and IFNγ. To discriminate between TH17 and TH1 cells in the CCR6+ subset, the authors found that within the CCR6+ subset CCR4 expression corresponded to TH17 cells and CXCR3 expression corresponded to TH1 cells (and the subset of T cells producing both IFNγ and IL-17). These CCR6+CCR4+ TH17-cell and CCR6+CXCR3+ TH1-cell phenotypes were shown to be stable even after stimulation in vitro.
To further characterize these TH17 cells, the authors turned their attention to the transcription factor RORγt (retinoic-acid-receptor-related orphan receptor-γt), which is known to be required for the differentiation of mouse TH17 cells. The levels of mRNA encoding the human orthologue of RORγt (RORC) were measured in each memory T-cell subset. Accordingly, RORC mRNA expression was restricted to the CCR6+CCR4+ TH17-cell subset, whereas expression of the TH1-cell-associated transcription factor T-bet was confined to the CXCR3+ TH1-cell subsets.
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