期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 60, 期 8, 页码 798-807出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1093/jnen/60.8.798
关键词
adhesion molecules; CD31; central nervous system; inflammation; PECAM-1; T cell
资金
- NHLBI NIH HHS [HL46849] Funding Source: Medline
- NINDS NIH HHS [NS 37570-01A2] Funding Source: Medline
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据