Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS‐infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell–astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca²⁺ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca²⁺ elevation through glial purinergic P2X7 receptor activation by the hemichannel‐dependent nucleotide release mechanism. Astrocyte Ca²⁺ increase is specifically triggered by the autoreactive CD4⁺ T‐cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca²⁺ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell–astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.

中文翻译：

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中枢神经系统浸润的免疫细胞通过星形胶质细胞嘌呤能信号诱导星形胶质细胞钙增加。

自身反应性免疫细胞和星形胶质细胞之间的相互作用是促进多发性硬化症神经变性的病理过程的重要组成部分。在这种炎症性疾病中，免疫细胞进入中枢神经系统 (CNS) 并通过 CNS 实质扩散，但这些自身反应性免疫细胞对星形胶质细胞活动模式的影响尚未确定。通过利用培养中的幼稚星形胶质细胞和从患有实验性自身免疫性脑脊髓炎 (EAE) 的大鼠中分离出的 CNS 浸润免疫细胞 (CNS IIC)，我们在这里展示了以前未被认识的免疫细胞-星形胶质细胞相互作用的特性。我们表明 CNS IICs 而不是外周免疫细胞应用，引起快速而有力的细胞内 Ca ²⁺通过促进神经胶质释放 ATP 增加星形胶质细胞。ATP通过半通道依赖性核苷酸释放机制激活神经胶质嘌呤能 P2X7 受体来促进Ca ²⁺升高。星形胶质细胞 Ca ²⁺增加是由自身反应性 CD4 ⁺ T 细胞应用触发的，这两种细胞类型在 EAE 中表现出密切的空间相互作用。因此，Ca ²⁺信号可能介导对局部环境中自身反应性免疫细胞的快速星形胶质细胞反应。免疫细胞-星形胶质细胞相互作用的这种特性在询问 CNS 自身免疫疾病的研究中可能很重要。