Chen Xin, Subleski Jeffrey J, Kopf Heather, Howard O M Zack, Männel Daniela N, Oppenheim Joost J
Basic Research Program, SAIC-Frederick Inc, National Cancer Institute (NCI)-Frederick, Frederick, MD 21702-1201, USA.
J Immunol. 2008 May 15;180(10):6467-71. doi: 10.4049/jimmunol.180.10.6467.
TNFR2 is predominantly expressed by a subset of human and mouse CD4(+)CD25(+)FoxP3(+) T regulatory cells (Tregs). In this study, we characterized the phenotype and function of TNFR2(+) Tregs in peripheral lymphoid tissues of normal and tumor-bearing C57BL/6 mice. We found that TNFR2 was expressed on 30-40% of the Tregs of the peripheral activated/memory subset that were most highly suppressive. In contrast, TNFR2(-) Tregs exhibited the phenotype of naive cells and only had minimal suppressive activity. Although not typically considered to be Tregs, CD4(+)CD25(-)TNFR2(+) cells nevertheless possessed moderate suppressive activity. Strikingly, the suppressive activity of TNFR2(+) Tregs was considerably more potent than that of reportedly highly suppressive CD103(+) Tregs. In the Lewis lung carcinoma model, more highly suppressive TNFR2(+) Tregs accumulated intratumorally than in the periphery. Thus, TNFR2 identifies a unique subset of mouse Tregs with an activated/memory phenotype and maximal suppressive activity that may account for tumor-infiltrating lymphocyte-mediated immune evasion by tumors.
肿瘤坏死因子受体2（TNFR2）主要由人和小鼠的一部分CD4(+)CD25(+)FoxP3(+)调节性T细胞（Tregs）表达。在本研究中，我们对正常和荷瘤C57BL/6小鼠外周淋巴组织中TNFR2(+) Tregs的表型和功能进行了表征。我们发现，TNFR2在最具抑制性的外周活化/记忆亚群的30%-40%的Tregs上表达。相比之下，TNFR2(-) Tregs表现出幼稚细胞的表型，并且只有最小的抑制活性。尽管通常不被认为是Tregs，但CD4(+)CD25(-)TNFR2(+)细胞仍具有中等抑制活性。令人惊讶的是，TNFR2(+) Tregs的抑制活性比据报道具有高度抑制性的CD103(+) Tregs的抑制活性强得多。在Lewis肺癌模型中，肿瘤内积累的具有更高抑制性的TNFR2(+) Tregs比外周更多。因此，TNFR2识别出具有活化/记忆表型和最大抑制活性的小鼠Tregs的一个独特亚群，这可能解释了肿瘤浸润淋巴细胞介导的肿瘤免疫逃逸。
