IFN-γ shapes immune invasion of the central nervous system via regulation of chemokines
IFN-γ shapes immune invasion of the central nervous system via regulation of chemokines
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DOI：
10.4049/jimmunol.164.5.2759
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发表时间：
2000-03-01
影响因子：
4.4
通讯作者：
Owens, T
中科院分区：
文献类型：
--
作者：
Tran, EH;Prince, EN;Owens, T
细胞因子和趋化因子之间的动态相互作用引导白细胞亚群在自身免疫性炎症中向组织迁移。我们研究了干扰素 -γ在实验性自身免疫性脑脊髓炎（EAE）中对趋化因子产生以及白细胞向中枢神经系统浸润的导向作用。BALB/c和C57BL/6小鼠对髓鞘碱性蛋白免疫诱导的EAE具有抵抗力。然而，干扰素 -γ缺陷型（BALB/c）和干扰素 -γ受体缺陷型（C57BL/6）小鼠却发展为快速进展的致死性疾病。可见脊髓广泛脱髓鞘以及弥散性白细胞浸润，这与SJL/J小鼠的局灶性血管周围浸润不同。中枢神经系统中以Gr - 1⁺中性粒细胞为主，还存在具有活化表型（CD69⁺，CD25⁺）的CD4⁺ T细胞以及嗜酸性粒细胞。正常情况下在EAE中上调的RANTES和巨噬细胞趋化蛋白 - 1在干扰素 -γ和干扰素 -γ受体缺陷型小鼠中无法检测到。巨噬细胞炎性蛋白 - 2和T细胞活化基因 - 3这两种吸引中性粒细胞的趋化因子则强烈上调。没有诱导产生Th2细胞因子IL - 4、IL - 10或IL - 13。核糖核酸酶保护试验和逆转录 - 聚合酶链反应显示，在患有EAE的干扰素 -γ或干扰素 -γ受体缺陷型小鼠中，IL - 2、IL - 3和IL - 15普遍存在，但IL - 12p40 mRNA水平没有升高。来自干扰素 -γ缺陷型小鼠的淋巴结细胞对髓鞘碱性蛋白有增殖反应，而BALB/c淋巴结细胞则没有。这些发现表明干扰素 -γ在EAE中具有调节作用，影响T细胞增殖并指导趋化因子产生，对疾病的发生和进展具有深远意义。
Dynamic interplay between cytokines and chemokines directs trafficking of leukocyte subpopulations to tissues in autoimmune inflammation. We have examined the role of IFN-gamma in directing chemokine production and leukocyte infiltration to the CNS in experimental autoimmune encephalomyelitis (EAE). BALB/c and C57BL/6 mice are resistant to induction of EAE by immunization with myelin basic protein. However, IFN-gamma-deficient (BALB/c) and IFN-gamma R-deficient (C57BL/6) mice developed rapidly progressing lethal disease. Widespread demyelination and disseminated leukocytic infiltration of spinal cord were seen, unlike the focal perivascular infiltrates in SJL/J mice. Gr-1(+) neutrophils predominated in CNS, and CD4(+) T cells with an activated (CD69(+), CD25(+)) phenotype and eosinophils were also present. RANTES and macrophage chemoattractant protein-1, normally up-regulated in EAE, were undetectable in IFN-gamma- and IFN-gamma R-deficient mice. Macrophage inflammatory protein-2 and T cell activation gene-3, both neutrophil-attracting chemokines, were strongly up-regulated. There was no induction of the Th2 cytokines, IL-4, IL-10, or IL-13. RNase protection assays and RT-PCR showed the prevalence of IL-2, IL-3, and IL-15, but no increase in IL-12p40 mRNA levels in IFN-gamma- or IFN-gamma R-deficient mice with EAE. Lymph node cells from IFN-gamma-deficient mice proliferated in response to myelin basic protein, whereas BALB/c lymph node cells did not. These findings show a regulatory role for IFN-gamma in EAE, acting on T cell proliferation and directing chemokine production, with profound implications for the onset and progression of disease.