Liu Hong, Rohowsky-Kochan Christine
Department of Neurology and Neurosciences, University of Medicine and Dentistry New Jersey-New Jersey Medical School, Newark, NJ 07103, USA.
J Immunol. 2008 Jun 15;180(12):7948-57. doi: 10.4049/jimmunol.180.12.7948.
IL-17-secreting T cells represent a distinct CD4(+) effector T cell lineage (Th17) that appears to be essential in the pathogenesis of numerous inflammatory and autoimmune diseases. Although extensively studied in the murine system, human Th17 cells have not been well characterized. In this study, we identify CD4(+)CD45RO(+)CCR7(-)CCR6(+) effector memory T cells as the principal IL-17-secreting T cells. Human Th17 cells have a unique cytokine profile because the majority coexpress TNF-alpha but not IL-6 and a minor subset express IL-17 with IL-22 or IL-17 and IFN-gamma. We demonstrate that the cytokines that promote the differentiation of human naive T cells into IL-17-secreting cells regulate IL-17 production by memory T cells. IL-1beta alone or in association with IL-23 and IL-6 markedly increase IL-17(+) CCR6(+) memory T cells and induce IL-17 production in CCR6(-) memory T cells. We also show that T cell activation induces Foxp3 expression in T cells and that the balance between the percentage of Foxp3(+) and IL-17(+) T cells is inversely influenced by the cytokine environment. These studies suggest that the cytokine environment may play a critical role in the expansion of memory T cells in chronic autoimmune diseases.
分泌白细胞介素-17（IL-17）的T细胞代表一种独特的CD4(+)效应T细胞谱系（Th17），它似乎在众多炎症性和自身免疫性疾病的发病机制中至关重要。尽管在小鼠系统中已得到广泛研究，但人类Th17细胞尚未得到充分表征。在本研究中，我们确定CD4(+)CD45RO(+)CCR7(-)CCR6(+)效应记忆T细胞是主要的分泌IL-17的T细胞。人类Th17细胞具有独特的细胞因子谱，因为大多数细胞共表达肿瘤坏死因子-α（TNF-α）而不表达白细胞介素-6（IL-6），并且一小部分亚群表达IL-17与白细胞介素-22（IL-22）或IL-17与干扰素-γ（IFN-γ）。我们证明，促进人类初始T细胞分化为分泌IL-17细胞的细胞因子可调节记忆T细胞产生IL-17。单独的IL-1β或与IL-23和IL-6联合使用可显著增加IL-17(+)CCR6(+)记忆T细胞，并诱导CCR6(-)记忆T细胞产生IL-17。我们还表明，T细胞活化可诱导T细胞中叉头框蛋白3（Foxp3）的表达，并且Foxp3(+)和IL-17(+)T细胞百分比之间的平衡受到细胞因子环境的反向影响。这些研究表明，细胞因子环境可能在慢性自身免疫性疾病中记忆T细胞的扩增中起关键作用。
