Role of autoreactive Tc17 cells in the pathogenesis of experimental autoimmune encephalomyelitis  

作　　者：Yong Peng Xiuli Zhang Yandan Tang Shunqing He Guilan Rao Quan Chen Yahui Xue Hong Jin Shu Liu Ziyang Zhou Yun Xiang 

机构地区：[1]Department of Neurology,Affliated First Hospitalof HunanTraditional Chinese Medical College,Zhuzhou,Hunan,China [2]Department of Neurology,The Third Affiliated Hospital of Hunan University of Chinese Medicine,Zhuzhou,Hunan,China [3]Science and Technology Innovation Center,HunanUniversityof ChineseMedicine,Changsha,Hunan,China

出　　处：《Neuroprotection》2024年第1期49-59,共11页神经保护（英文）

基　　金：Scientific Research Project of Hunan Provincial Health Commission,Grant/Award Number:C2023030765;University-Hospital Joint-Fund of Hunan University of Chinese Medicine,Grant/Award Number:2022XYLH198;Key Plans of Hunan Administration Traditional Chinese Medicine,Grant/Award Number:A2023039;Technology Plan Project of Zhuzhou City,Hunan Province,Grant/Award Number:2021-009;Fund for Creative Research Group of Affiliated First Hospital of Hunan Traditional Chinese Medical College,Grant/Award Number:2021 B-003。

摘　　要：Background:The pathogenesis of multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE-an animal model of MS)is primarily mediated by T cells.However,recent studies have only focused on interleukin(IL)-17-secreting CD4^(+)T-helper cells,also known as Th17 cells.This study aimed to compare Th17 cells and IL-17-secreting CD8^(+)T-cytotoxic cells(Tc17)in the context of MS/EAE.Methods:Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides 35-55(MOG35-55),pertussis toxin,and complete Freund's adjuvant to establish the EAE animal model.T cells were isolated from the spleen(12-14 days postimmunization).CD4^(+)and CD8^(+)T cells were purified using isolation kit and then differentiated into Th17 and Tc17,respectively,using MOG35-55 and IL-23.The secretion levels of interferon-(IFN-γ)and IL-17 were measured via enzyme-linked immunosorbent assay using cultured CD4^(+)and CD8^(+)T cell supernatants.The pathogenicity of Tc17 and Th17 cells was assessed through adoptive transfer(tEAE),with the clinical course assessed using an EAE score(0-5).Hematoxylin and eosin as well as Luxol fast blue staining were used to examine the spinal cord.Purified CD8^(+)CD3^(+)and CD4^(+)CD3^(+)cells differentiated into Tc17 and Th17 cells,respectively,were stimulated with MOG35-55 peptide for proliferation assays.Results:The results showed that Tc17 cells(15,951±19855VS.55,709±4196cpm;p<0.050)exhibited a weaker response to highest dose(20μg/mL)MOG35-55 than Th17 cells.However,this response was not dependent on Th17 cells.After the 48h stimulation,at the highest dose(20μg/mL)of MOG35-55.Tc17 cells secreted lower levels of IFN-(280.00±15.00vs.556.67±15.28pg/mL,p<0.050)and IL-17(102.67±5.86 pg/mL vs.288.33±12.58 pg/mL;p<0.050)than Th17 cells.Similar patterns were observed for IFN-γsecretion at 96 and 144h.Furthermore,Tc17 cell-induced tEAE mice exhibited similar EAE scores to Th17 cell-induced tEAE mice and also showed similar inflammation and demyelination.Conclusion:The degree of pathogenic

关 键 词：CD8^(+)T cells experimental autoimmune myelitis IFN-y IL-17 multiple sclerosis Tc17 cells 

分 类 号：R744.3[医药卫生—神经病学与精神病学]