Characterization of myelin oligodendrocyte glycoprotein (MOG)35-55-specific CD8+ T cells in experimental autoimmune encephalomyelitis
10.1097/CM9.0000000000000551
- Author:
Peng YONG
1
;
Zhu FEI-ZHOU
;
Chen ZHI-XING
;
Zhou JIAN-XIONG
;
Gan LU
;
Yang SHAN-SHAN
;
Gao SHUAI
;
Liu QIAN-QIAN
Author Information
1. Department of Neurology
- Keywords:
Autoimmune;
CD8-Positive T-Lymphocytes;
Encephalomyelitis;
Experimental;
Multiple Sclerosis;
Myelin-Oligodendrocyte Glycoprotein
- From:
Chinese Medical Journal
2019;132(24):2934-2940
- CountryChina
- Language:Chinese
-
Abstract:
Background:The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells,but most studies of MS and its animal model,experimental autoimmune encephalomyelitis (EAE),have focused on CD4+ T cells.The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE.Methods:Female C57BL/6 mice (n=20) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide.At 14 days after immunization,T cells were isolated from the spleen and purified as CD4+ and CD8+ T cells by using CD4 and CD8 isolation kits,and then the purity was determined by flow cytometric analysis.These cells were stimulated by MOG35-55 peptide and applied to proliferation assays.The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4+ and CD8+ T cells were measured by enzyme-linked immunosorbent assays (ELISA).For adoptive transfer,recipient mice were injected with MOG35-55-specific CD8+ or CD4+ T cells.EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.Results:CD8+CD3+ and CD4+CD3+ cells were 86% and 94% pure of total CD3+ cells after CD8/CD4 bead enrichment,respectively.These cells were stimulated by MOG35-55 peptide and applied to proliferation assays.Although the CD8+ T cells had a generally lower response to MOG35-55 than CD4+ T cells,the response of CD8+ T cells was not always dependent on CD4.CD8+ T cell secreted less IFN-γ and IL-4 compared with CD4+ T cells.EAE was induced in wildtype B6 na(i)ve mice by adoptive transfer of MOG35-55-specific T cells from B6 active-induced EAE (aEAE) mice.A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8+ T cells from immunized B6 mice compared with transfer of CD4+ T cells.Conclusion:Our data suggest that CD8+ autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4+ counterparts.