Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses
Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses
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DOI：
10.1158/0008-5472.can-05-1319
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发表时间：
2005-09-15
期刊：
影响因子：
11.2
通讯作者：
Vicari, AP
中科院分区：
文献类型：
--
作者：
Dercamp, C;Chemin, K;Vicari, AP
缺乏抗肿瘤免疫通常与CD8 T细胞反应受损有关，这可能是由于肿瘤浸润树突状细胞（TIDC）的启动能力差或调节性T细胞（T-reg）的进一步抑制。白细胞介素-10 （IL-10）与TIDC的抑制以及T-reg的产生和功能有关。在这里，我们讨论了IL-10和CD25(+) T-reg在CD8抗肿瘤免疫中的一些各自和可能重叠的作用。虽然肿瘤抗原特异性CD8 T细胞在体内存在IL-10或T-reg时增殖，但在缺乏IL-10和T-reg的小鼠中观察到最佳的效应功能。事实上，在正常而非il -10缺失或cd25缺失小鼠中生长的肿瘤诱导肿瘤抗原特异性CD8抑制T细胞。抑制涉及转化生长因子- β。同样，IL-10和T-reg都是tidc对CD8 T细胞启动受损的原因，但tidc产生的IL-12仅被不依赖于T-reg的IL-10阻止。随后，需要IL-10缺陷和T-reg缺失来实现CpG激活后TIDC对CD8 t细胞效应物的最佳诱导。我们的研究结果指出了IL-10和T-reg在抑制tidc介导的抗肿瘤CD8 t细胞反应中的主要冗余和非冗余作用。
Lack of antitumor immunity is often related to impaired CD8 T-cell responses that could result from a poor priming capacity by tumor-infiltrating dendritic cells (TIDC) and or further inhibition by regulatory T cells (T-reg). Interleukin-10 (IL-10) has been implicated in the inhibition of TIDC as well as in the generation and functions of T-reg. Here, we address some of the respective and possibly overlapping roles of IL-10 and CD25(+) T-reg in CD8 antitumor immunity. Whereas tumor antigen-specific CD8 T cells proliferated in vivo in the presence of IL-10 or T-reg, optimal effector functions were observed in mice lacking both IL-10 and T-reg. Indeed, tumors grown in normal but not in IL-10-deficient or CD25-depleted mice induced tumor antigen-specific CD8 suppressor T cells. Suppression involved transforming growth factor-beta. Similarly, both IL-10 and T-reg were responsible for impaired CD8 T cell priming by TIDCs, but IL-12 production by TIDCs was prevented only by T-reg-independent IL-10. Subsequently, IL-10 defect and T-reg depletion were required to achieve optimal induction of CD8 T-cell effectors by TIDC following CpG activation. Our results point out major redundant and nonredundant roles for IL-10 and T-reg in the inhibition of TIDC-mediated generation of antitumor CD8 T-cell response.