Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide.
Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide.
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通过靶向独特的无引起的CD1D反应T细胞群体对硫化物的反应性，预防自身免疫性。
DOI：
10.1084/jem.20031389
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发表时间：
2004-04-05
影响因子：
15.3
通讯作者：
Kumar, V
中科院分区：
文献类型：
--
作者：
Jahng, A;Maricic, I;Aguilera, C;Cardell, S;Halder, RC;Kumar, V
针对髓鞘中存在的蛋白质的I类和II类MHC限制性T细胞已被证明参与中枢神经系统(CNS)的自身免疫。目前尚不清楚中枢神经系统中是否存在CD1d限制性T细胞对髓磷脂的反应，并可能作为影响自身免疫性脱髓鞘过程的靶点。利用特异性糖脂-CD1d四聚体和克隆的T细胞，我们鉴定了对CD1d提出的髓鞘衍生糖脂硫脂有反应的T细胞群。这一群体不同于不变的Vα14+NK T细胞，一组Vα3/Vα8+CD1d限制性NK T细胞杂交瘤在CD1d+抗原提呈细胞存在的情况下无法识别硫脂。有趣的是，在实验性自身免疫性脑脊髓炎(人类多发性硬化症的模型)期间，中枢神经系统组织中硫脂反应性T细胞而不是不变的NK T细胞增加了几倍。此外，用硫脂治疗小鼠可以预防野生型小鼠中抗原诱导的实验性自身免疫性脑脊髓炎，但不能预防CD1d缺陷小鼠。疾病预防与硫脂抑制致病髓鞘少突胶质细胞糖蛋白反应性T细胞产生干扰素-γ和白介素4的能力有关。由于CD1d限制性T细胞对硫脂的识别现已在小鼠和人类中得到证实，对小鼠髓磷脂反应T细胞的研究可能成为开发人类自身免疫性脱髓鞘疾病干预策略的基础。
Class I and class II MHC-restricted T cells specific for proteins present in myelin have been shown to be involved in autoimmunity in the central nervous system (CNS). It is not yet known whether CD1d-restricted T cells reactive to myelin-derived lipids are present in the CNS and might be targeted to influence the course of autoimmune demyelination. Using specific glycolipid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1d. This population is distinct from the invariant Vα14+ NK T cells, and a panel of Vα3/Vα8+ CD1d-restricted NK T cell hybridomas is unable to recognize sulfatide in the presence of CD1d+ antigen-presenting cells. Interestingly, during experimental autoimmune encephalomyelitis a model for human multiple sclerosis, sulfatide-reactive T cells but not invariant NK T cells are increased severalfold in CNS tissue. Moreover, treatment of mice with sulfatide prevents antigen-induced experimental autoimmune encephalomyelitis in wild-type but not in CD1d-deficient mice. Disease prevention correlates with the ability of sulfatide to suppress both interferon-γ and interleukin-4 production by pathogenic myelin oligodendrocyte glycoprotein-reactive T cells. Since recognition of sulfatide by CD1d-restricted T cells has now been shown both in mice and humans, study of murine myelin lipid-reactive T cells may form a basis for the development of intervention strategies in human autoimmune demyelinating diseases.
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DOI：
10.1084/jem.192.5.741
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
通讯作者：
Kronenberg M
影响因子：
15.3
作者：
Park, SH;Weiss, A;Bendelac, A
通讯作者：
Bendelac, A
DOI：
10.1073/pnas.92.21.9510
发表时间：
1995-10-10
影响因子：
11.1
作者：
KUMAR, V;BHARDWAJ, V;SERCARZ, E
通讯作者：
SERCARZ, E
DOI：
10.1084/jem.182.4.993
发表时间：
1995-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cardell S;Tangri S;Chan S;Kronenberg M;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
64.8
作者：
Miyamoto, K;Miyake, S;Yamamura, T
通讯作者：
Yamamura, T