Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury
Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury
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DOI：
10.1523/jneurosci.0305-05.2005
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发表时间：
2005-07-13
影响因子：
5.3
通讯作者：
Popovich, PG
中科院分区：
文献类型：
--
作者：
Jones, TB;Hart, RP;Popovich, PG
脊髓挫伤后协调T细胞迁移和激活的脊髓内线索用B10来表征。带有T细胞谱系的野生型和转基因(TG)小鼠倾向于识别髓鞘碱性蛋白(MBP)。在此之前，我们发现这些菌株表现出不同的解剖和行为表型。在Tg小鼠中，脊髓损伤(SCI)激活了MBP反应性T细胞，导致比非TgWild型小鼠更严重的轴突损伤、脱髓鞘和功能障碍(B10。PL)。相反，尽管B10中有强大的脊髓损伤诱导的T细胞反应。未见明显的T细胞介导的病理改变。在这里，我们展示了慢性脊髓内T细胞在B10中的积聚。PL和TG小鼠CXCL10/IP-10和CCL5/RANTES的mRNA表达显著和持续增加。然而，在转基因小鼠中，趋化因子mRNA的水平比B10高2-17倍。并与脊髓内T细胞加速内流和整个脊髓内中枢神经系统巨噬细胞激活增强有关。这些数据表明，在小鼠脊髓损伤后，启动T细胞反应的常见分子途径；然而，如果T细胞反应与MBP有偏见，神经炎症的分子和细胞决定因素会随着神经病理和功能损害的加重而放大。
The intraspinal cues that orchestrate T-cell migration and activation after spinal contusion injury were characterized using B10. PL ( wild-type) and transgenic (Tg) mice with a T-cell repertoire biased toward recognition of myelin basic protein (MBP). Previously, we showed that these strains exhibit distinct anatomical and behavioral phenotypes. In Tg mice, MBP-reactive T-cells are activated by spinal cord injury (SCI), causing more severe axonal injury, demyelination, and functional impairment than is found in non-Tgwild-type mice ( B10. PL). Conversely, despite a robust SCI-induced T-cell response in B10. PL mice, no overt T-cell-mediated pathology was evident. Here, we show that chronic intraspinal T-cell accumulation in B10. PL and Tg mice is associated with a dramatic and sustained increase in CXCL10/IP-10 and CCL5/RANTES mRNA expression. However, in Tg mice, chemokine mRNA were enhanced 2- to 17-fold higher than in B10. PL mice and were associated with accelerated intraspinal T-cell influx and enhanced CNS macrophage activation throughout the spinal cord. These data suggest common molecular pathways for initiating T-cell responses after SCI in mice; however, if T-cell reactions are biased against MBP, molecular and cellular determinants of neuroinflammation are magnified in parallel with exacerbation of neuropathology and functional impairment.