CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses
CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses
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DOI：
10.1073/pnas.1834479100
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发表时间：
2003-09-16
影响因子：
11.1
通讯作者：
Shiku, H
中科院分区：
文献类型：
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作者：
Nishikawa, H;Kato, T;Shiku, H
通过重组表达克隆（SEREX）（一种血清学表达克隆方法）对抗原进行血清学鉴定，已经通过肿瘤携带者血清中的IgG抗体定义了多种肿瘤衍生抗原。这些抗原中的大多数没有显示出结构异常，似乎是野生型自身抗原。用编码这些自身抗原和肿瘤特异性细胞毒性T淋巴细胞表位的DNA共免疫增强了CD 8（+）T细胞应答，并以CD 4（+）T细胞依赖性方式增加了对肿瘤攻击的抵抗力。相比之下，单独用这些SEREX定义的自身抗原免疫导致对肿瘤攻击的易感性增加。免疫的这种抑制作用由CD 4（+）CD 25（+）T细胞介导。在用SEREX定义的自身抗原之一DNA J样2免疫的小鼠中，在肺室中α-GalCer/CD 1d四聚体（+）CD 3（+）T细胞[代表自然杀伤T（NKT）细胞]的数量减少，而未观察到其他T细胞亚群数量的明显变化。用缺乏大多数NKT细胞的Jalpha 281（-/-）小鼠进行的实验表明，NKT细胞主要负责转移抑制，并且它们的活性被用DNA J样2免疫抑制。我们认为SEREX鉴定了一组自身抗原，这些抗原通过CD 4（+）CD 25（+）调节性T细胞维持和调节免疫稳态。
A variety of tumor-derived antigens have been defined by IgG antibodies in tumor bearers' sera with serological identification of antigens by recombinant expression cloning (SEREX), a serological expression cloning method. The majority of these antigens show no structural abnormality and seem to be wild-type autoantigens. Coimmunization with DNA encoding these autoantigens and tumor-specific cytotoxic T lymphocytes epitopes heightened CD8(+) T cell responses and increased resistance to tumor challenge in a CD4(+) T cell-dependent manner. In contrast, immunization with these SEREX-defined autoantigens alone leads to heightened susceptibility to tumor challenge. This suppressive effect of immunization is mediated by CD4(+) CD25(+) T cells. In mice immunized with one of the SEREX-defined autoantigens, Dna J-like 2, the number of alpha-GalCer/CD1d tetramer(+) CD3(+) T cells [representing natural killer T (NKT) cells] was reduced in the pulmonary compartment, whereas no evident change in the number of other T cell subsets was observed. Experiments with Jalpha281(-/-) mice lacking most NKT cells indicate that NKT cells are primarily responsible for metastasis suppression and that their activity is inhibited by immunization with Dna J-like 2. We propose that SEREX identifies a pool of autoantigens that maintains and regulates immunological homeostasis via CD4(+) CD25(+) regulatory T cells.