Department of Medicine, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2010 Jan 14;5(1):e8706. doi: 10.1371/journal.pone.0008706.
IL-9 is a growth factor for T- and mast-cells that is secreted by human Th2 cells. We recently reported that IL-4+TGF-beta directs mouse CD4(+)CD25(-)CD62L(+) T cells to commit to inflammatory IL-9 producing CD4(+) T cells.
METHODOLOGY/PRINCIPAL FINDINGS: Here we show that human inducible regulatory T cells (iTregs) also express IL-9. IL-4+TGF-beta induced higher levels of IL-9 expression in plate bound-anti-CD3 mAb (pbCD3)/soluble-anti-CD28 mAb (sCD28) activated human resting memory CD4(+)CD25(-)CD45RO(+) T cells as compared to naïve CD4(+)CD25(-)CD45RA(+) T cells. In addition, as compared to pbCD3/sCD28 plus TGF-beta stimulation, IL-4+TGF-beta stimulated memory CD4(+)CD25(-)CD45RO(+) T cells expressed reduced FOXP3 protein. As analyzed by pre-amplification boosted single-cell real-time PCR, human CD4(+)IL-9(+) T cells expressed GATA3 and RORC, but not IL-10, IL-13, IFNgamma or IL-17A/F. Attempts to optimize IL-9 production by pbCD3/sCD28 and IL-4+TGF-beta stimulated resting memory CD4(+) T cells demonstrated that the addition of IL-1beta, IL-12, and IL-21 further enhance IL-9 production.
CONCLUSIONS/SIGNIFICANCE: Taken together these data show both the differences and similarities between mouse and human CD4(+)IL9(+) T cells and reaffirm the powerful influence of inflammatory cytokines to shape the response of activated CD4(+) T cells to antigen.
白细胞介素 9（IL-9）是一种生长因子，可促进 T 细胞和肥大细胞的生长，由人类 Th2 细胞分泌。我们最近报道称，IL-4+TGF-β可促使小鼠 CD4+CD25-CD62L+T 细胞向炎症性的产生白细胞介素 9 的 CD4+T 细胞分化。
方法/主要发现：在这里，我们发现人类诱导性调节性 T 细胞（iTregs）也表达白细胞介素 9（IL-9）。与初始 CD4+CD25-CD45RA+T 细胞相比，IL-4+TGF-β在平板结合抗-CD3 mAb（pbCD3）/可溶性抗-CD28 mAb（sCD28）激活的人类静止记忆 CD4+CD25-CD45RO+T 细胞中诱导更高水平的 IL-9 表达。此外，与 pbCD3/sCD28+TGF-β刺激相比，IL-4+TGF-β刺激记忆 CD4+CD25-CD45RO+T 细胞表达的 FOXP3 蛋白减少。通过预扩增增强的单细胞实时 PCR 分析，人类 CD4+IL-9+T 细胞表达 GATA3 和 RORC，但不表达 IL-10、IL-13、IFNγ或 IL-17A/F。尝试优化 pbCD3/sCD28 和 IL-4+TGF-β 刺激的静止记忆 CD4+T 细胞的白细胞介素 9 产生，结果表明添加白细胞介素 1β、白细胞介素 12 和白细胞介素 21 可进一步增强白细胞介素 9 的产生。
结论/意义：综上所述，这些数据显示了小鼠和人类 CD4+IL9+T 细胞之间的差异和相似之处，并再次证实了炎症细胞因子对激活的 CD4+T 细胞对抗原反应的强大影响。
