Cytotoxic T lymphocyte antigen 4 (CD152) regulates self-reactive T cells in BALB/c but not in the autoimmune NOD mouse.
Cytotoxic T lymphocyte antigen 4 (CD152) regulates self-reactive T cells in BALB/c but not in the autoimmune NOD mouse.
复制标题
细胞毒性 T 淋巴细胞抗原 4 (CD152) 在 BALB/c 中调节自身反应性 T 细胞，但在自身免疫 NOD 小鼠中则不然。
DOI：
10.1006/jaut.1999.0353
复制
发表时间：
2000
影响因子：
12.8
通讯作者：
Haskins,K
中科院分区：
文献类型：
--
作者：
Piganelli,JD;Poulin,M;Martin,T;Allison,JP;Haskins,K
最近的研究表明，细胞毒性T淋巴细胞抗原4 (CTLA-4)/ CD152对T细胞产生抑制信号，阻止正在进行的免疫反应。由于异常的CD152活性被认为有助于自身免疫，我们研究了CD152介导的抑制信号对自身免疫、糖尿病易发NOD和非自身免疫性BALB/c小鼠对自身和外源抗原反应的影响。在小鼠免疫自身抗原、同源胰岛细胞或外源抗原、钥匙孔帽贝血青素（KLH）之前和之后，用抗CD152阻断抗体处理小鼠，阻止CD152与其配体B7的相互作用。与对照抗体处理的小鼠相比，CD152阻断BALB/c小鼠刺激了强大的胰岛特异性T细胞介导的免疫反应。在BALB/c小鼠中，T细胞反应的增强与CD152作为T细胞激活反应的下调因子的作用一致。此外，CD152阻断在非自身免疫性BALB/c小鼠中揭示了胰岛细胞特异性自身反应性T细胞。相反，CD152阻断在NOD小鼠中未能调节胰岛特异性自身反应性T细胞反应。然而，在非自身免疫性BALB/c和自身免疫性NOD小鼠中，CD152阻断增强了T细胞对外源性外源抗原KLH的反应。总的来说，这些结果表明，NOD自身免疫小鼠中cd152介导的外周T细胞免疫反应调节并不存在全局缺陷，而是一种特异性的T细胞识别自身抗原的缺陷。
Recent studies demonstrated that engagement of cytotoxic T lymphocyte antigen 4 (CTLA-4)/(CD152) generates an inhibitory signal to T cells which arrests an on-going immune response. Since aberrant CD152 activity is thought to contribute to autoimmunity, we examined the effect of CD152-mediated inhibitory signals on the response to self and foreign antigens in autoimmune, diabetes-prone NOD and non-autoimmune BALB/c mice. The interaction of CD152 with its ligand B7 was prevented by treating the mice with anti-CD152 blocking antibody, before and following immunization of the mice with the self-antigen, syngeneic islet cells, or the foreign antigen, key-hole limpet hemocyanin (KLH). CD152 blockade in BALB/c mice stimulated a robust islet-specific T cell-mediated immune response compared to control antibody-treated mice. The augmentation of T cell responses in BALB/c mice was consistent with the role proposed for CD152 as a down-regulator of T cell activation responses. Furthermore, CD152 blockade unmasked islet cell specific autoreactive T cells in the non-autoimmune BALB/c mouse. Conversely, CD152 blockade in NOD mice failed to regulate islet-specific auto-reactive T cell responses. However, CD152 blockade enhanced the T cell response to the exogenous, foreign antigen KLH in both non-autoimmune BALB/c and autoimmune NOD mice. Collectively, these results suggest that there is not a global defect in CD152-mediated regulation of peripheral T cell immune responses in NOD autoimmune mice but rather, a defect specific to T cells recognizing self antigen.