Gammadelta T cells in EAE: early trafficking events and cytokine requirements.
Gammadelta T cells in EAE: early trafficking events and cytokine requirements.
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DOI：
10.1002/eji.200839176
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发表时间：
2009-06
影响因子：
5.4
通讯作者：
Barnum, Scott R.
中科院分区：
文献类型：
--
作者：
Wohler, Jillian E.;Smith, Sherry S.;Zinn, Kurt R.;Bullard, Dan C.;Barnum, Scott R.
我们先前已经证明，在EAE期间，γδT细胞向中枢神经系统转运，同时β2-整合素的表达增加，并产生干扰素-γ和肿瘤坏死因子-α。为了扩展这些研究，我们将生物发光的γδT细胞转移到野生型小鼠，并跟踪它们在疾病急性阶段的运动。我们发现γδT细胞迅速迁移到注射髓鞘少突胶质细胞糖蛋白多肽的部位，并经历了大量的扩增。在诱发EAE后的6天内，在脊髓和脑中发现了生物发光的γδT细胞，在第10天到第12天达到高峰，然后在第15天迅速下降。γδT细胞−/−小鼠与γδ2整合素缺陷小鼠(CD11a、-b或-c)来源的βT细胞的重组表明，γδT细胞在EAE期间向中枢神经系统的转运不依赖于这一家族的黏附分子。我们还检测了γδT细胞产生的干扰素-γ和肿瘤坏死因子-α在EAE中的作用，发现γδT细胞产生这两种细胞因子是全面发展EAE所必需的。这些结果表明γδT细胞在EAE的发生发展中起关键作用，并提示脱髓鞘疾病的治疗靶点。
We have previously shown that γδ T cells traffic to the CNS during EAE with concurrent increased expression of β2-integrins and production of IFN-γ and TNF-α. To extend these studies, we transferred bioluminescent γδ T cells to wild type mice and followed their movement through the acute stages of disease. We found that γδ T cells rapidly migrated to the site of myelin oligodendrocyte glycoprotein (MOG) peptide injection and underwent massive expansion. Within six days after EAE induction, bioluminescent γδ T cells were found in the spinal cord and brain, peaking in number between days ten and twelve and then rapidly declining by day fifteen. Reconstitution of γδ T cell−/− mice with γδ T cells derived from β2-integrin-deficient mice (CD11a, -b or -c) demonstrated that γδ T cell trafficking to the CNS during EAE is independent of this family of adhesion molecules. We also examined the role of γδ T cell-produced IFN-γ and TNF-α in EAE and found that production of both cytokines by γδ T cells was required for full development of EAE. These results indicate that γδ T cells are critical for the development of EAE and suggest a therapeutic target in demyelinating disease.
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