PMID- 28197337
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2050-0068 (Print)
IS  - 2050-0068 (Electronic)
IS  - 2050-0068 (Linking)
VI  - 6
IP  - 1
DP  - 2017 Jan
TI  - Defective T-cell control of Epstein-Barr virus infection in multiple sclerosis.
PG  - e126
LID - 10.1038/cti.2016.87 [doi]
AB  - Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a 
      major role in the pathogenesis of multiple sclerosis (MS). Defective elimination 
      of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected 
      autoreactive B cells to accumulate in the brain. Here we undertake a 
      comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry 
      and intracellular IFN-gamma staining to measure T-cell responses to EBV-infected 
      autologous lymphoblastoid cell lines and pools of human leukocyte antigen 
      (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and 
      cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects. 
      In 20 HLA-A2(+) healthy subjects and 20 HLA-A2(+) patients we also analysed 
      CD8(+) T cells specific for individual peptides, measured by binding to 
      HLA-peptide complexes and production of IFN-gamma, TNF-alpha and IL-2. We found a 
      decreased CD8(+) T-cell response to EBV lytic, but not CMV lytic, antigens at the 
      onset of MS and at all subsequent disease stages. CD8(+) T cells directed against 
      EBV latent antigens were increased but had reduced cytokine polyfunctionality 
      indicating T-cell exhaustion. During attacks the EBV-specific CD4(+) and CD8(+) 
      T-cell populations expanded, with increased functionality of latent-specific 
      CD8(+) T cells. With increasing disease duration, EBV-specific CD4(+) and CD8(+) 
      T cells progressively declined, consistent with T-cell exhaustion. The anti-EBNA1 
      IgG titre correlated inversely with the EBV-specific CD8(+) T-cell frequency. We 
      postulate that defective CD8(+) T-cell control of EBV reactivation leads to an 
      expanded population of latently infected cells, including autoreactive B cells.
FAU - Pender, Michael P
AU  - Pender MP
AD  - School of Medicine, The University of Queensland, Brisbane, Queensland, 
      Australia; Department of Neurology, Royal Brisbane and Women's Hospital, 
      Brisbane, Queensland, Australia; Cellular ImmunoIogy Laboratory, QIMR Berghofer 
      Medical Research Institute, Brisbane, Queensland, Australia.
FAU - Csurhes, Peter A
AU  - Csurhes PA
AD  - School of Medicine, The University of Queensland, Brisbane, Queensland, 
      Australia; Cellular ImmunoIogy Laboratory, QIMR Berghofer Medical Research 
      Institute, Brisbane, Queensland, Australia; The University of Queensland Centre 
      for Clinical Research, Brisbane, Queensland, Australia.
FAU - Burrows, Jacqueline M
AU  - Burrows JM
AD  - Cellular ImmunoIogy Laboratory, QIMR Berghofer Medical Research Institute , 
      Brisbane, Queensland, Australia.
FAU - Burrows, Scott R
AU  - Burrows SR
AD  - School of Medicine, The University of Queensland, Brisbane, Queensland, 
      Australia; Cellular ImmunoIogy Laboratory, QIMR Berghofer Medical Research 
      Institute, Brisbane, Queensland, Australia.
LA  - eng
PT  - Journal Article
DEP - 20170120
PL  - Australia
TA  - Clin Transl Immunology
JT  - Clinical & translational immunology
JID - 101638268
EIN - Clin Transl Immunology. 2017 Jun 16;6(6):e147. PMID: 28748090
PMC - PMC5292561
COIS- The authors declare no conflict of interest.
EDAT- 2017/02/16 06:00
MHDA- 2017/02/16 06:01
PMCR- 2017/01/01
CRDT- 2017/02/16 06:00
PHST- 2016/09/21 00:00 [received]
PHST- 2016/12/02 00:00 [revised]
PHST- 2016/12/02 00:00 [accepted]
PHST- 2017/02/16 06:00 [entrez]
PHST- 2017/02/16 06:00 [pubmed]
PHST- 2017/02/16 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - cti201687 [pii]
AID - 10.1038/cti.2016.87 [doi]
PST - epublish
SO  - Clin Transl Immunology. 2017 Jan 20;6(1):e126. doi: 10.1038/cti.2016.87. 
      eCollection 2017 Jan.