Ford Mandy L, Evavold Brian D
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Cell Immunol. 2006 Mar;240(1):53-61. doi: 10.1016/j.cellimm.2006.06.007. Epub 2006 Aug 7.
Several recent reports have described an effector role for CD8(+) T cells during EAE. We have previously demonstrated reduced disease incidence and severity in CD43(-/-) mice following MOG immunization, and attributed this attenuation in disease progression to the effects of CD43 deficiency on CD4+ T cells. Here, we extend those studies to examine the effects of the loss of CD43 on MOG-specific CD8+ T cells. A reduced frequency of MOG-specific CD8+ T cells following immunization was observed in CD43(-/-) mice relative to wild-type controls, as demonstrated by intracellular cytokine and MHC tetramer staining. In addition, adoptive transfer of CD8+ MOG 35-55-primed LN cells from CD43(-/-) mice resulted in significantly attenuated EAE induction as compared to recipients of wild-type CD8+ MOG-primed cells. Analysis of intracellular signaling intermediates revealed a deficiency in the ability of MOG-specific CD8+ T cells to phosphorylate ERK in response to antigen. These results characterize an important role for CD43 during the activation and expansion of autoreactive MOG-specific CD8+ T cells.
最近的几份报告描述了CD8(+) T细胞在实验性自身免疫性脑脊髓炎(EAE)中的效应作用。我们之前已经证明,在髓鞘少突胶质细胞糖蛋白(MOG)免疫后,CD43(-/-)小鼠的疾病发病率和严重程度降低,并将疾病进展的这种减弱归因于CD43缺乏对CD4+ T细胞的影响。在此,我们扩展这些研究以检查CD43缺失对MOG特异性CD8+ T细胞的影响。通过细胞内细胞因子和MHC四聚体染色证明,与野生型对照相比,在CD43(-/-)小鼠中观察到免疫后MOG特异性CD8+ T细胞的频率降低。此外,与野生型CD8+ MOG预致敏细胞的受体相比,来自CD43(-/-)小鼠的CD8+ MOG 35-55预致敏淋巴结细胞的过继转移导致EAE诱导明显减弱。细胞内信号转导中间体的分析揭示,MOG特异性CD8+ T细胞响应抗原磷酸化细胞外信号调节激酶(ERK)的能力存在缺陷。这些结果表明CD43在自身反应性MOG特异性CD8+ T细胞的激活和扩增过程中起重要作用。