Immunosurveillance of Erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance
Immunosurveillance of Erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance
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DOI：
10.1158/0008-5472.can-06-1432
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发表时间：
2006-08-01
期刊：
影响因子：
11.2
通讯作者：
Cavallo, Federica
中科院分区：
文献类型：
--
作者：
Ambrosino, Elena;Spadaro, Michela;Cavallo, Federica
为了评估CD 4（+）CD 25（+）Foxp 3（+）调节性T（Treg）细胞在克服Erbb 2（HER-2/neu）乳腺病变的免疫监视中的作用，我们研究了持续去除它们对BALB/c雌性小鼠的影响，这些小鼠为大鼠Erbb 2（r-Erbb 2）癌基因转基因小鼠（BALB-neuT小鼠），其发展为多发性乳腺癌。在这些病变的进展过程中，Treg细胞在脾脏、肿瘤引流淋巴结和肿瘤中扩增。抗CD 25抗体的重复给药延长了无肿瘤生存期，降低了癌的多样性，并导致天然抗体和CTL介导的针对r-Erbb 2的反应性的表现。抗CD 25治疗期间Foxp 3（+）Treg细胞的丢失显著导致Gr 1（+）未成熟髓样细胞的消失，表明这两种抑制性免疫细胞类型之间存在串扰。与r-Erbb 2过表达相关的Treg细胞扩增可被视为抑制由自身抗原的局部异常过表达引起的免疫反应的生理反应。
To assess the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in overcoming immunosurveillance of Erbb2 (HER-2/neu) mammary lesions, we studied the effects of their sustained removal in BALB/c female mice made transgenic for the rat Erbb2 (r-Erbb2) oncogene (BALB-neuT mice), which develop multiple mammary carcinomas. During the progression of these lesions, Treg cells expand in the spleen, tumor draining lymph nodes, and tumors. Repeated administration of anti-CD25 antibodies extends tumor-free survival, reduces carcinoma multiplicity, and leads to the manifestation of a natural antibody and CTL-mediated reactivity against r-Erbb2. Loss of Foxp3(+) Treg cells during anti-CD25 treatment remarkably caused the disappearance of Gr1(+) immature myeloid cells, suggesting a cross-talk between these two inhibitory immune cell types. Treg cell expansion associated with r-Erbb2 overexpression may be seen as a physiologic response to dampen the immune reaction elicited by local anomalous overexpression of a self-antigen.