CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation
CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation
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DOI：
10.1523/jneurosci.5276-03.2004
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发表时间：
2004-05-05
影响因子：
5.3
通讯作者：
Jones, KJ
中科院分区：
文献类型：
--
作者：
Byram, SC;Carson, MJ;Jones, KJ
我们的实验室发现免疫系统的CD4阳性（CD4(+)） T细胞向受损的小鼠面部运动神经元（FMNs）传递短暂的神经保护（Serpe et al., 1999,2000,2003）。神经保护机制中的一个基本问题涉及作为抗原呈递细胞（APC）激活CD4(+) T细胞的细胞的身份。在这里，我们首先确定CD4(+) T细胞对非中枢神经系统抗原的反应不能支持FMN的存活，其次，证明了CD4(+) T细胞激活的双室模型。小鼠骨髓（BM）嵌合体分别在中央区室和外周区室中表达主要组织相容性复合体II的常驻抗原呈递宿主细胞和BM来源的抗原呈递供体细胞之间进行了区分。面神经横断后，单独的两个隔室都不足以导致激活CD4(+) T细胞介导的FMN存活。相反，CD4(+) T细胞介导的神经保护似乎依赖于中央隔室的常驻小胶质细胞和外周隔室的bm来源的APC。这是第一个在体内的报告，证明了一种神经保护机制需要APC功能的常驻（即实质）小胶质细胞。
Our laboratory discovered that CD4-positive (CD4(+)) T cells of the immune system convey transitory neuroprotection to injured mouse facial motoneurons (FMNs) (Serpe et al., 1999, 2000, 2003). A fundamental question in the mechanisms responsible for neuroprotection concerns the identity of the cell(s) that serves as the antigen-presenting cell (APC) to activate the CD4(+) T cells. Here, we first establish that CD4(+) T cells reactive to non-CNS antigen fail to support FMN survival and, second, demonstrate a two-compartment model of CD4(+) T cell activation. Mouse bone marrow (BM) chimeras were developed that discriminate between resident antigen-presenting host cell and BM-derived antigen-presenting donor cell expression of major histocompatibility complex II within central and peripheral compartments, respectively. After facial nerve transection, neither compartment alone is sufficient to result in activated CD4(+) T cell-mediated FMN survival. Rather, CD4(+) T cell-mediated neuroprotection appears to depend on both resident microglial cells in the central compartment and a BM-derived APC in the peripheral compartment. This is the first in vivo report demonstrating a neuroprotective mechanism requiring APC functions by resident (i.e., parenchymal) microglial cells.