CD8 T 细胞在发热伴血小板减少综合征中介导抗病毒反应。

CD8 T cells mediate antiviral response in severe fever with thrombocytopenia syndrome.

机构信息

Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, China.

Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

FASEB J. 2023 Jan;37(1):e22722. doi: 10.1096/fj.202201343RR.

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by a novel Bunyavirus, has gradually become a threatening infectious disease in rural areas of Asia. Studies have identified a severe cytokine storm and impaired humoral immune response in SFTS. However, the cellular immune response to SFTS virus (SFTSV) infection remains largely unknown. Here we report that SFTS patients had a cytokine storm accompanied by high levels of chemokines. CD8 T cells in peripheral blood mononuclear cells of SFTS patients exhibited a more activated phenotype and enhanced the antiviral responses. They increased the expression of CD69 and CD25, secreted a higher level of IFN-γ and granzyme, and had a stronger proliferative ability than in healthy controls. In convalescent SFTS patients, the expression of CD69 and CD25 on CD8 T cells was reduced. In addition, we found the ratio and cellularity of CD14 CD16 intermediate monocytes were increased in peripheral blood of SFTS patients. Both the expression of C-X-C motif chemokine ligand 10 (CXCL10) on CD14 CD16 intermediate monocytes and the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD8 T cells increased dramatically in SFTS patients. Our studies reveal a potential pathway that CD8 T cells rapidly activate and are mostly recruited by intermediate monocytes through CXCL10 in SFTSV infection. Our results may be of clinical relevance for further treatment and discharge instructions in SFTSV infections.

摘要

严重发热伴血小板减少综合征(SFTS)是由一种新型布尼亚病毒引起的,已逐渐成为亚洲农村地区具有威胁性的传染病。研究发现,SFTS 存在严重的细胞因子风暴和体液免疫应答受损。然而,SFTS 病毒(SFTSV)感染的细胞免疫应答仍知之甚少。在这里,我们报告 SFTS 患者存在细胞因子风暴,伴有趋化因子水平升高。SFTS 患者外周血单个核细胞中的 CD8 T 细胞表现出更活化的表型,并增强了抗病毒反应。它们增加了 CD69 和 CD25 的表达,分泌更高水平的 IFN-γ 和颗粒酶,并具有比健康对照更强的增殖能力。在康复的 SFTS 患者中,CD8 T 细胞上的 CD69 和 CD25 的表达减少。此外,我们发现 SFTS 患者外周血中 CD14 CD16 中间单核细胞的比例和细胞数增加。SFTS 患者 CD14 CD16 中间单核细胞上的 C-X-C 基序趋化因子配体 10(CXCL10)表达和 CD8 T 细胞上的 C-X-C 基序趋化因子受体 3(CXCR3)表达均显著增加。我们的研究揭示了一条潜在的途径,即在 SFTSV 感染中,CD8 T 细胞通过 CXCL10 迅速激活并主要由中间单核细胞募集。我们的研究结果可能对 SFTSV 感染的进一步治疗和出院指示具有临床相关性。

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