Functional and pathogenic differences of Th1 and Th17 cells in experimental autoimmune encephalomyelitis.
Functional and pathogenic differences of Th1 and Th17 cells in experimental autoimmune encephalomyelitis.
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DOI：
10.1371/journal.pone.0015531
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发表时间：
2010-11-29
期刊：
影响因子：
3.7
通讯作者：
Krishnamoorthy G
中科院分区：
文献类型：
--
作者：
Domingues HS;Mues M;Lassmann H;Wekerle H;Krishnamoorthy G
人们一致认为，实验性自身免疫性脑脊髓炎（EAE）可以由Th1和Th17表型的髓磷脂特异性T细胞介导，但这两种亚群对致病过程的贡献仍然存在争议。在本报告中，我们比较了识别髓鞘少突胶质细胞糖蛋白（MOG）的“单克隆”T细胞系的功能差异和致病潜力，这些T细胞系具有相同的转基因TCR，但通过IFN-γ产生th1样和IL-17产生th17样细胞因子特征来区分。CD4+ T细胞系来源于转基因小鼠2D2株，该株表达在I-Ab环境下识别MOG肽35-55的TCR。将Th1细胞过继转移到淋巴细胞减少（Rag2−/−）受体中，主要诱导“典型”麻痹性EAE，而在大约50%的受体动物中，Th17细胞介导“非典型”失调性EAE。Th1和Th17细胞的联合作用增强了经典EAE的脑致生性。Th1和Th17介导的EAE病变的组成不同，但在中枢神经系统内的定位没有差异。虽然Th1病变中含有IFN-γ，但没有产生IL-17的T细胞，但Th17病变中的T细胞表现出可塑性，大量转化为产生IFN-γ的Th1样细胞。Th1和Th17细胞的裂解潜能有很大的不同。Th1而非Th17细胞在体外以接触依赖的方式裂解自身抗原呈递星形胶质细胞和成纤维细胞。相比之下，Th17细胞只有在抗原刺激并转化为产生Th1表型的IFN-γ后才获得细胞毒性潜能。我们的数据表明，Th1和Th17谱系都具有诱导中枢神经系统自身免疫的能力，但可以通过互补和差异致病机制发挥作用。我们提出产生IL-17的th17样细胞是产生非典型EAE所必需的，而产生IFN-γ的Th1细胞则诱导经典EAE。
There is consensus that experimental autoimmune encephalomyelitis (EAE) can be mediated by myelin specific T cells of Th1 as well as of Th17 phenotype, but the contribution of either subset to the pathogenic process has remained controversial. In this report, we compare functional differences and pathogenic potential of “monoclonal” T cell lines that recognize myelin oligodendrocyte glycoprotein (MOG) with the same transgenic TCR but are distinguished by an IFN-γ producing Th1-like and IL-17 producing Th17-like cytokine signature. CD4+ T cell lines were derived from the transgenic mouse strain 2D2, which expresses a TCR recognizing MOG peptide 35–55 in the context of I-Ab. Adoptive transfer of Th1 cells into lymphopenic (Rag2−/−) recipients, predominantly induced “classic” paralytic EAE, whereas Th17 cells mediated “atypical” ataxic EAE in approximately 50% of the recipient animals. Combination of Th1 and Th17 cells potentiated the encephalitogenicity inducing classical EAE exclusively. Th1 and Th17 mediated EAE lesions differed in their composition but not in their localization within the CNS. While Th1 lesions contained IFN-γ, but no IL-17 producing T cells, the T cells in Th17 lesions showed plasticity, substantially converting to IFN-γ producing Th1-like cells. Th1 and Th17 cells differed drastically by their lytic potential. Th1 but not Th17 cells lysed autoantigen presenting astrocytes and fibroblasts in vitro in a contact-dependent manner. In contrast, Th17 cells acquired cytotoxic potential only after antigenic stimulation and conversion to IFN-γ producing Th1 phenotype. Our data demonstrate that both Th1 and Th17 lineages possess the ability to induce CNS autoimmunity but can function with complementary as well as differential pathogenic mechanisms. We propose that Th17-like cells producing IL-17 are required for the generation of atypical EAE whereas IFN-γ producing Th1 cells induce classical EAE.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1084/jem.181.1.381
发表时间：
1995-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Leonard JP;Waldburger KE;Goldman SJ
通讯作者：
Goldman SJ
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.
DOI：
10.1084/jem.20080159
发表时间：
2008-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kroenke MA;Carlson TJ;Andjelkovic AV;Segal BM
通讯作者：
Segal BM
影响因子：
3.3
作者：
BARTEN, DM;RUDDLE, NH
通讯作者：
RUDDLE, NH