Inhibition of antigen-specific T cell trafficking into the central nervous system via blocking PECAM1/CD31 molecule
Inhibition of antigen-specific T cell trafficking into the central nervous system via blocking PECAM1/CD31 molecule
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DOI：
10.1093/jnen/60.8.798
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发表时间：
2001-08-01
影响因子：
3.2
通讯作者：
Fabry, Z
中科院分区：
文献类型：
--
作者：
Qing, Z;Sandor, M;Fabry, Z
抗原特异性T细胞进入中枢神经系统（CNS）是大脑炎症的重要起始步骤。尽管对粘附分子在T细胞跨周血管迁移中的作用有广泛的了解，但抗原特异性T细胞进入中枢神经系统的机制尚不清楚。这项工作旨在研究粘附分子在抗原特异性T细胞迁移到中枢神经系统中的调节作用。抗原特异性T细胞在体内迁移试验中被追踪，使用T细胞受体（TCR）转基因小鼠，具有95%的T细胞特异性抗原，鸽细胞色素c （PCC）。将转TCR转基因小鼠置入脑室内（IVT）进行PCC抗原输注和脑脊液（CSF）取样。PCC输注到中枢神经系统后。在抗黏附分子试剂存在或不存在的情况下，脑脊液中α / β TCR+ V β (3+) Mac1（-）细胞的数量。我们发现了针对VCAM-1 （CD106）的抗体。VLA-4 (CD49d/CD29), ICAM-1 （CD54）。lfa -1 （CD11a/CD18）和lfa -1 （CD11a/CD18）不影响脑脊液中抗原特异性T细胞数量的增加，但经静脉注射后，抗pecam -1 （CD31）抗体或PECAM-Ig嵌合分子抑制了α / β TCR+ V β (3+) Mac I -细胞进入中枢神经系统的运输。在体外抗原刺激下，pecam - 1 （CD31）在抗原特异性T细胞上的表达也以时间依赖性的方式上调。通过CD44和lfa - 1表达来测量体内抗原诱导的T细胞活化，发现在mpecamig处理小鼠和野生型血清对照处理组之间具有可比性。这表明CD31抑制抗原特异性T细胞在中枢神经系统的积累可能不是由于这些细胞的功能抑制。最后，将cfse标记的和转基因细胞过继转移到幼稚动物体内，导致PCC IVT免疫后这些细胞在中枢神经系统中积累，这也被mPECAMIg处理抑制。因此，PECAM-1 （CD31）可能在调节CNS炎症性疾病中抗原特异性T细胞运输中发挥重要作用。
Trafficking of antigen-specific T cells into the central nervous system (CNS) is an important initiating step in inflammation in the brain. In spite of the extensive knowledge about the role of adhesion molecules in T cell migration across peripheral vessels, the mechanism of the entry of antigen-specific T cells into the CNS is not known. This work was designed to study the regulatory roles of adhesion molecules in antigen-specific T cell migration into the CNS. Antigen-specific T cells were tracked in an in vivo migration assay using T cell receptor (TCR) transgenic mice having 95% of T cells specific for a defined antigen, pigeon cytochrome c (PCC). TCR transgenic mice were cannulated intraventricularly (IVT) for PCC antigen infusion and cerebrospinal fluid (CSF) sampling. Upon PCC infusion into the CNS. the number of alpha/beta TCR+ V beta (3+) Mac1(-)cells in the CSF was characterized in the presence or absence of anti-adhesion molecule reagents. We found that antibodies against VCAM-1 (CD106). VLA-4 (CD49d/CD29), ICAM-1 (CD54). and LFA-l (CD11a/CD18) did not influence the increased number of antigen-specific T cells in the CSF However, upon intravenous (IV) injection, anti-PECAM-1 (CD31) antibody or PECAM-Ig chimeric molecule inhibited the trafficking of alpha/beta TCR+ V beta (3+) Mac I - cells into the CNS. The expression of PECAM-I (CD31) was also up-regulated on antigen-specific T cells in a time-dependent manner in vitro upon antigenic stimulation. The antigen-induced activation of T cells in vivo was measured by CD44 and LFA-I expression and found to be comparable between mPECAMIg-treated mice and wild-type ser-um control-treated groups. This indicates that CD31 inhibition of antigen-specific T cell accumulation in the CNS is probably not due to a functional inhibition of these cells. Finally, adoptive transfer of CFSE-labeled AND transgenic cells into naive animals resulted in the accumulation of these cells in the CNS upon PCC IVT immunization that was also inhibited by mPECAMIg treatment. Hence, PECAM-1 (CD31) might play an important role in regulating antigen-specific T cells trafficking in CNS inflammatory diseases.