Larmonier Nicolas, Marron Marilyn, Zeng Yi, Cantrell Jessica, Romanoski Angela, Sepassi Marjan, Thompson Sylvia, Chen Xinchun, Andreansky Samita, Katsanis Emmanuel
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA.
Cancer Immunol Immunother. 2007 Jan;56(1):48-59. doi: 10.1007/s00262-006-0160-8. Epub 2006 Apr 13.
CD4(+)CD25(+) regulatory T cells have been characterized as a critical population of immunosuppressive cells. They play a crucial role in cancer progression by inhibiting the effector function of CD4(+) or CD8(+) T lymphocytes. However, whether regulatory T lymphocytes that expand during tumor progression can modulate dendritic cell function is unclear. To address this issue, we have evaluated the inhibitory potential of CD4(+)CD25(+) regulatory T cells from mice bearing a BCR-ABL(+) leukemia on bone marrow-derived dendritic cells. We present data demonstrating that CD4(+)CD25(+)FoxP3(+) regulatory T cells from tumor-bearing animals impede dendritic cell function by down-regulating the activation of the transcription factor NF-kappaB. The expression of the co-stimulatory molecules CD80, CD86 and CD40, the production of TNF-alpha, IL-12, and CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression mechanism requires TGF-beta and IL-10 and is associated with induction of the Smad signaling pathway and activation of the STAT3 transcription factor.
CD4(+)CD25(+)调节性T细胞已被确认为免疫抑制细胞的关键群体。它们通过抑制CD4(+)或CD8(+)T淋巴细胞的效应功能，在癌症进展中发挥关键作用。然而，肿瘤进展过程中扩增的调节性T淋巴细胞是否能够调节树突状细胞功能尚不清楚。为了解决这一问题，我们评估了携带BCR-ABL(+)白血病的小鼠体内CD4(+)CD25(+)调节性T细胞对骨髓来源的树突状细胞的抑制潜能。我们提供的数据表明，荷瘤动物的CD4(+)CD25(+)FoxP3(+)调节性T细胞通过下调转录因子NF-κB的激活来阻碍树突状细胞功能。被抑制的树突状细胞上共刺激分子CD80、CD86和CD40的表达以及TNF-α、IL-12和CCL5/RANTES的产生均被强烈下调。抑制机制需要转化生长因子-β（TGF-β）和白细胞介素-10（IL-10），并与Smad信号通路的诱导和信号转导及转录激活因子3（STAT3）转录因子的激活相关。
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