Concurrent induction of antitumor immunity and autoimmune thyroiditis in CD4+CD25+ regulatory T cell-depleted mice
Concurrent induction of antitumor immunity and autoimmune thyroiditis in CD4+CD25+ regulatory T cell-depleted mice
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DOI：
10.1158/0008-5472.can-05-0934
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发表时间：
2005-09-15
期刊：
影响因子：
11.2
通讯作者：
Kong, YCM
中科院分区：
文献类型：
--
作者：
Wei, WZ;Jacob, WB;Kong, YCM
当CD 4（+）CD 25（+）调节性T细胞被耗尽或失活以增强抗肿瘤免疫时，自身免疫性疾病的风险可能显著升高，因为这些调节性T细胞控制抗肿瘤免疫和自身免疫。为了评估调节CD 4（+）CD 25（+）调节性T细胞的相对益处和风险，我们建立了一种新的测试系统，以同时测量对肿瘤相关抗原neu和不相关的自身抗原甲状腺球蛋白的免疫反应性。BALB/c小鼠接种表达活化的大鼠neu的TUBO细胞，并用抗CD 25单克隆抗体处理以去除CD 25（+）细胞。肿瘤生长，然后消退，并诱导neu特异性抗体和IFN-γ分泌T细胞。同样的小鼠也通过长期静脉注射暴露于小鼠甲状腺球蛋白。这些小鼠产生甲状腺球蛋白特异性抗体和IFN-γ分泌T细胞，一些小鼠的甲状腺中有炎症浸润。在TUBO肿瘤排斥和甲状腺球蛋白注射的小鼠中，对neu或甲状腺球蛋白的免疫反应比单独使用的小鼠更强。据我们所知，这是第一个实验系统，以评估的同时诱导和可能的协同作用的免疫反应性定义的肿瘤和自身抗原减少调节性T细胞。这些结果说明了在涉及免疫调节剂的癌症免疫治疗期间监测对自身抗原的免疫反应性的重要性，以及迫切需要新的策略来诱导抗肿瘤免疫同时最小化自身免疫。
When CD4(+)CD25(+) regulatory T cells are depleted or inactivated for the purpose of enhancing antitumor immunity, the risk of autoimmune disease may be significantly elevated because these regulatory T cells control both antitumor immunity and autoimmunity. To evaluate the relative benefit and risk of modulating CD4(+)CD25(+) regulatory T cells, we established a new test system to measure simultaneously the immune reactivity to a tumor-associated antigen, neu, and an unrelated self-antigen, thyroglobulin. BALB/c mice were inoculated with TUBO cells expressing an activated rat neu and treated with anti-CD25 monoclonal antibody to deplete CD25(+) cells. The tumors grew, then regressed, and neu-specific antibodies and IFN-gamma-secreting T cells were induced. The same mice were also exposed to mouse thyroglobulin by chronic i.v. injections. These mice produced thyroglobulin-specific antibody and IFN-gamma-secreting T cells with inflammatory infiltration in the thyroids of some mice. The immune responses to neu or thyroglobulin were greater in mice undergoing TUBO tumor rejection and thyroglobulin injection than in those experiencing either alone. To the best of our knowledge, this is the first experimental system to assess the concurrent induction and possible synergy of immune reactivity to defined tumor and self-antigens following reduction of regulatory T cells. These results illustrate the importance of monitoring immune reactivity to self-antigens during cancer immunotherapy that involves immunomodulating agents, and the pressing need for novel strategies to induce antitumor immunity while minimizing autoimmunity.