Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance
Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance
复制标题
DOI：
10.1038/ni988
复制
发表时间：
2003-11-01
影响因子：
30.5
通讯作者：
Kuchroo, VK
中科院分区：
文献类型：
--
作者：
Sabatos, CA;Chakravarti, S;Kuchroo, VK
1型辅助性T细胞（Th1）免疫应答在细胞介导的免疫中起核心作用，并且一种被称为Tim - 3（T细胞免疫球蛋白结构域，黏蛋白结构域）的Th1特异性细胞表面分子已被确定。在此我们报道一种分泌形式的Tim - 3的鉴定结果，它仅包含全长分子的免疫球蛋白（Ig）可变（V）结构域。两种Tim - 3异构体的融合蛋白（Tim - 3 - Ig）都能特异性结合CD4⁺T细胞，这表明在CD4⁺T细胞上表达一种Tim - 3配体。给免疫后的小鼠施用Tim - 3 - Ig会导致Th1细胞过度增殖以及Th1细胞因子释放。Tim - 3 - Ig还会消除Th1细胞中的耐受诱导，并且Tim - 3缺陷型小鼠对高剂量耐受的诱导具有抵抗性。这些数据表明，在正常免疫应答过程中，Tim - 3与Tim - 3配体的相互作用可能起到抑制效应Th1细胞的作用，并且对于外周耐受的诱导可能至关重要。
T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.