Larmonier Nicolas, Cantrell Jessica, Lacasse Collin, Li Gang, Janikashvili Nona, Situ Elaine, Sepassi Marjan, Andreansky Samita, Katsanis Emmanuel
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA.
J Leukoc Biol. 2008 Apr;83(4):1049-59. doi: 10.1189/jlb.0907635. Epub 2008 Jan 3.
CD4(+)CD25(+) regulatory T lymphocytes (Tregs) critically contribute to the mechanisms of cancer-induced tolerance. These cells suppress anti-tumoral CD8(+) and CD4(+) T lymphocytes and can also restrain the function of APCs. We have previously documented the immunostimulatory effects of a chaperone-rich cell lysate (CRCL) anti-cancer vaccine. Tumor-derived CRCL induces tumor immunity in vivo, partly by promoting dendritic cell (DC) and macrophage activation. In the current study, we evaluated the effects of CD4(+)CD25(+)forkhead box P3(+) Tregs isolated from mice bearing 12B1 bcr-abl(+) leukemia on DC and macrophages that had been activated by 12B1-derived CRCL. CRCL-activated DC and macrophages resisted Treg suppression, as the production of proinflammatory cytokines, the activation of transcription factor NF-kappaB, and their immunostimulatory potential was unaffected by Tregs. Our results thus highlight CRCL as a powerful adjuvant endowed with the capacity to overcome tumor-induced Treg-inhibitory effects on APCs.
CD4(+)CD25(+)调节性T淋巴细胞（Tregs）对癌症诱导的耐受机制起着关键作用。这些细胞可抑制抗肿瘤的CD8(+)和CD4(+) T淋巴细胞，还能限制抗原呈递细胞（APC）的功能。我们之前记录了富含伴侣蛋白的细胞裂解物（CRCL）抗癌疫苗的免疫刺激作用。肿瘤来源的CRCL在体内诱导肿瘤免疫，部分是通过促进树突状细胞（DC）和巨噬细胞的活化。在当前研究中，我们评估了从携带12B1 bcr-abl(+)白血病的小鼠中分离出的CD4(+)CD25(+)叉头框P3(+) Tregs对由12B1来源的CRCL激活的DC和巨噬细胞的影响。CRCL激活的DC和巨噬细胞抵抗Treg的抑制作用，因为促炎细胞因子的产生、转录因子NF-κB的激活及其免疫刺激潜力不受Tregs的影响。因此，我们的结果突出了CRCL作为一种强大的佐剂，具有克服肿瘤诱导的Tregs对APC抑制作用的能力。
