Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor
Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor
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DOI：
10.1016/j.immuni.2007.04.017
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发表时间：
2007-07-01
期刊：
影响因子：
32.4
通讯作者：
Sakaguchi, Shimon
中科院分区：
文献类型：
--
作者：
Yamaguchi, Tomoyuki;Hirota, Keiji;Sakaguchi, Shimon
免疫应答可以通过表达Foxp 3的CD 25（+）CD 4（+）天然调节性T（Treg）细胞相对于其他初始或活化T细胞的差异操作来增强或抑制。通过寻找能够区分这些群体的分子，我们发现天然Treg细胞组成性表达大量的叶酸受体4（FR 4）。FR 4和CD 25的表达还将抗原刺激的CD 4+非Treg细胞分离成FR 4（hi）CD 25（-）和FR 4（lo）CD 25（+）群体，其在再刺激后的增殖和细胞因子分泌方面不同。这些区别表明，抗原刺激激活和扩增抗原特异性天然Treg细胞以及效应和记忆T细胞。因此，从同种异体抗原刺激的T细胞富集的FR 4（hi）CD 25（+）CD 4（+）T细胞抑制移植物排斥。FR 4单克隆抗体的施用特异性地减少了Treg细胞，在荷瘤动物中激发了有效的肿瘤免疫，而正常年轻小鼠的类似治疗引起了自身免疫性疾病。因此，FR 4（hi）CD 25（+）CD 4（+）Treg细胞的特异性操作有助于控制正在进行的免疫应答。
Immune responses can be enhanced or dampened by differential manipulation of Foxp3-expressing CD25(+)CD4(+) natural regulatory T (Treg) cells versus other naive or activated T cells. By searching for a molecule capable of distinguishing these populations, we here found that natural Treg cells constitutively expressed high amounts of folate receptor 4 (FR4). The expression of FR4 and CD25 also separated antigen-stimulated CD4+ non-Treg cells into the FR4(hi)CD25(-) and FR4(lo)CD25(+) populations, which were different in proliferation and cytokine secretion upon restimulation. These distinctions showed that antigenic stimulation activated and expanded antigen-specific natural Treg cells as well as effector and memory T cells. Accordingly, FR4(hi)CD25(+)CD4(+) T cells enriched from alloantigen-stimulated T cells suppressed graft rejection. Administration of FR4 monoclonal antibody specifically reduced Treg cells, provoking effective tumor immunity in tumor-bearing animals, whereas similar treatment of normal young mice elicited autoimmune disease. Thus, specific manipulation of FR4(hi)CD25(+) CD4(+) Treg cells helps control ongoing immune responses.