A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse.

A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse.
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DOI:
10.4049/jimmunol.157.2.941
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发表时间:
1996-07
影响因子:
4.4
通讯作者:
A. J. Rajan;Yan-ling Gao;C. S. Raine;C. Brosnan
A. J. Rajan;Yan-ling Gao;C. S. Raine;C. Brosnan
中科院分区:
医学2区
文献类型:
--
作者:
A. J. Rajan;Yan-ling Gao;C. S. Raine;C. Brosnan

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先前的研究已经在多发性硬化症和实验性过敏性脑脊髓炎(EAE)病变中检测到γ δ T细胞,但它们的作用仍然不清楚。在本研究中,我们评估了复发缓解型EAE小鼠脾脏和中枢神经系统(CNS)中的γ δ T细胞动力学和分布,并研究了使用mAb GL 3消除这些细胞对疾病临床和病理表达的影响。通过免疫组织化学和流式细胞仪分析,在中枢神经系统中的γ δ T细胞群中观察到显著的疾病相关变化。FACS分析显示,尽管γ δ T细胞在所有阶段在脾脏中保持低水平(约占总CD 3 + T细胞的2%),但在CNS中,它们在急性发作高峰时增加至约12%,在恢复期下降至约5%,但在慢性期再次上升至约12%。在γ δ T细胞在急性疾病发作前即刻或慢性阶段耗尽的动物中,观察到临床体征严重程度显著降低,这与CNS中CD 3 +/γ δ T细胞百分比降低相关。在耗竭动物中,在急性期观察到炎症和脱髓鞘的统计学显著减少,但在慢性期仅发现对这些疾病参数的边际影响。总之,数据支持以下结论:在疾病过程的急性和慢性/进行性阶段,γ δ T细胞在小鼠EAE的发病机制中起重要作用。
Previous studies have detected gamma delta T cells in multiple sclerosis and experimental allergic encephalomyelitis (EAE) lesions but their role remains obscure. In the present study, we assessed gamma delta T cell dynamics and distribution in spleen and central nervous system (CNS) from mice with relapsing-remitting EAE, and studied the effect of depleting these cells on clinical and pathologic expression of disease using the mAb GL3. By immunohistochemistry and FACS analysis, striking disease-related changes were observed in the gamma delta T cell population in the CNS. FACS analysis showed that while gamma delta T cells remained low in the spleen (approximately 2% total CD3+ T cells) at all stages, in the CNS they increased to approximately 12% at the height of the acute attack, fell to approximately 5% during the recovery phase, but rose again to approximately 12% during the chronic phase. In animals in which gamma delta T cells were depleted immediately before the onset of acute disease, or during the chronic stage, a striking and significant reduction in the severity of the clinical signs was observed that was associated with a decrease in the percentage of CD3+/gamma delta T cells in the CNS. In depleted animals a statistically significant reduction in inflammation and demyelination was noted during the acute stage, but only marginal effects on these disease parameters were found in the chronic phase. Taken together, the data support the conclusion that gamma delta T cells play an important role in the pathogenesis of EAE in mice during both acute and chronic/progressive phases of the disease process.