Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function.
Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function.
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DOI：
10.1084/jem.20062498
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发表时间：
2007-07-09
期刊：
影响因子：
--
通讯作者：
Kuchroo VK
中科院分区：
文献类型：
--
作者：
Xiao S;Najafian N;Reddy J;Albin M;Zhu C;Jensen E;Imitola J;Korn T;Anderson AC;Zhang Z;Gutierrez C;Moll T;Sobel RA;Umetsu DT;Yagita H;Akiba H;Strom T;Sayegh MH;DeKruyff RH;Khoury SJ;Kuchroo VK
有研究表明，T细胞上表达的T细胞免疫球蛋白粘蛋白(TIM)-1具有积极的共刺激T细胞反应的作用。然而，TIM-1通过其配体TIM-4的交联导致T细胞反应的激活或抑制，从而引发了TIM-1是否具有双重共刺激功能的问题。为了解决这个问题，我们测试了一系列针对TIM-1的单抗，并鉴定了两种功能相反的抗体。一种抗TIM-1抗体增加了抗原特异性T细胞的频率，增加了促炎细胞因子干扰素-γ和IL-17的产生，并增加了实验性自身免疫性脑脊髓炎的严重程度。相反，另一种抗TIM-1抗体抑制抗原特异性T细胞的产生、干扰素-γ和IL-17的产生以及自身免疫的发展，并引起强烈的Th2型反应。这两种抗体都与TIM-1分子免疫球蛋白结构域中密切相关的表位结合，但激活抗体对TIM-1的亲和力是抑制性抗体的17倍。虽然两种抗TIM-1抗体都能诱导CD3封顶，但只有激活抗体能引起强烈的细胞骨架重组和运动。这些数据表明，TIM-1调节T细胞的反应，TIM-1的参与可以改变T细胞的功能，这取决于它所参与的亲和力/亲和力。
It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specific for Tim-1 and identified two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specific T cells, the production of the proinflammatory cytokines IFN-γ and IL-17, and the severity of experimental autoimmune encephalomyelitis. In contrast, another anti–Tim-1 antibody inhibited the generation of antigen-specific T cells, production of IFN-γ and IL-17, and development of autoimmunity, and it caused a strong Th2 response. Both antibodies bound to closely related epitopes in the IgV domain of the Tim-1 molecule, but the activating antibody had an avidity for Tim-1 that was 17 times higher than the inhibitory antibody. Although both anti–Tim-1 antibodies induced CD3 capping, only the activating antibody caused strong cytoskeletal reorganization and motility. These data indicate that Tim-1 regulates T cell responses and that Tim-1 engagement can alter T cell function depending on the affinity/avidity with which it is engaged.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
2.7
作者：
Chae, SC;Song, JH;Chung, HT
通讯作者：
Chung, HT
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82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
11.4
作者：
Kaplan, G;Totsuka, A;Feinstone, SM
通讯作者：
Feinstone, SM
影响因子：
64.5
作者：
KUCHROO, VK;DAS, MP;GLIMCHER, LH
通讯作者：
GLIMCHER, LH