Cross-reactivity of autoreactive T cells with MBP and viral antigens in patients with MS.
In this study, we detected the viral DNA of Human Herpes Virus 6 (HHV-6) in the sera and cell-free cerebrospinal fluid (CSF) of Chinese multiple sclerosis (MS) patients. The results revealed that the copy numbers of serum HHV-6 viral DNA were higher in MS than in normal subjects (NS) or in other neurologic diseases (OND). We also found that in the MS subjects, most T cells recognizing myelin basic protein (MBP) were cross-reactive and could be activated by a synthetic peptide corresponding to residues of HHV-6 or EBV. The estimated precursor frequency of these cross-reactive T cells recognizing both peptides, MBP and HHV-6 or EBV, was significantly elevated in MS compared with that in controls. More significant was the presence of CD8+ cytotoxic cross-reactive T cells, as they could directly induce injury to oligodendrocytes that are known to express both MBP and MHC class I molecules. The study provides important evidence for understanding the potential role of HHV-6 or EBV infection in the pathogenesis of MS.
Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, 227 South Chongqing Road, Shanghai 200025, China.
Weizhi
W
Cheng
Yanhui
Y
Ma
Fang
F
Gong
Chaoying
C
Hu
Liu
L
Qian
Qiuyu
Q
Huang
Qiwen
Q
Yu
Jiying
J
Zhang
Shengdi
S
Chen
Zhengguo
Z
Liu
Xuehua
X
Chen
Tong
T
Zhou
Dongqing
D
Zhang
D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D016516:CD4-CD8 Ratio; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D004279:DNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D017931:DNA Primers; D004279:DNA, Viral