CD4+CD25+ regulatory T cells that secrete TGFβ and IL-10 are preferentially induced by a vaccine vector
CD4+CD25+ regulatory T cells that secrete TGFβ and IL-10 are preferentially induced by a vaccine vector
复制标题
DOI：
10.1097/00002371-200409000-00002
复制
发表时间：
2004-09-01
影响因子：
3.9
通讯作者：
Paterson, Y
中科院分区：
文献类型：
--
作者：
Hussain, SF;Paterson, Y
在疫苗方案中产生的CD 4（+）CD 25（+）T细胞可以在限制抗肿瘤治疗中发挥关键作用，因此对基于免疫疗法的癌症治疗具有广泛的意义。作者先前使用单核细胞增生李斯特菌开发了两种表达HPV-16 E7蛋白的疫苗构建体，并诱导对HPV-E7表达肿瘤的强细胞免疫。用Lm-LL 0-E7免疫小鼠，诱导肿瘤消退，而Lm-E7显示很少或没有肿瘤消退。为了研究调节性CD 4（+）CD 25（+）T细胞群可能是肿瘤消退差异的原因，作者描述了两种疫苗系统产生的这些细胞的作用。作者比较了荷瘤接种小鼠中CD 4（+）CD 25（+）T细胞的流行率，并证明与Lm-LLO-E7接种小鼠相比，Lm-E7接种小鼠的脾脏和肿瘤浸润淋巴细胞中CD 4（+）CD 25（+）T细胞数量显著增加。作者通过体外抑制试验证实，这些数量增加的CD 4（+）CD 25（+）T细胞确实具有抑制功能，并且肿瘤浸润细胞的作用机制涉及抑制细胞因子白细胞介素-10和转化生长因子β的产生。这些结果表明，肿瘤疫苗系统有可能产生肿瘤浸润性CD 4（+）CD 25（+）调节性T细胞，这些细胞对肿瘤消退和疫苗治疗的总体成功有重要影响。
CD4(+)CD25(+) T cells generated in a vaccine scenario can play a critical role in limiting antitumor therapy, thus having widespread implications for the immunotherapy-based treatment of cancer. The authors previously used Listeria monocytogenes to develop two vaccine constructs that express HPV-16 E7 protein and induce strong cellular immunity to HPV-E7-expressing tumors. Immunization of mice hearing established E7-expressing tumors with Lm-LLO-E7 induced regression of the tumors, whereas Lm-E7 showed little or no tumor regression. To investigate the possibility that regulatory CD4(+)CD25(+) T-cell populations may be responsible for the differences in tumor regression, the authors characterized the role of these cells generated by the two vaccine systems. The authors compared the prevalence of CD4(+)CD25(+) T cells in tumor-bearing vaccinated mice and demonstrate that Lm-E7-vaccinated mice have significantly increased numbers of CD4(+)CD25(+) T cells in both the spleen and tumor-infiltrating lymphocytes compared with Lm-LLO-E7-vaccinated mice. The authors confirm that these increased numbers of CD4(+)CD25(+) T cells are indeed suppressor in function by in vitro suppression assays and that the mechanism of action of the tumor-infiltrating cells involves the production of suppressor cytokines interleukin-10 and transforming growth factor beta. These results show that it is possible for a tumor vaccine system to generate tumor-infiltrating CD4(+)CD25(+) regulatory T cells that critically affect tumor regression and the overall success of vaccine therapy.