PMID- 26041797
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 22
IP  - 3
DP  - 2016 Mar
TI  - Intrathecal CD8 T-cells of multiple sclerosis patients recognize lytic 
      Epstein-Barr virus proteins.
PG  - 279-91
LID - 10.1177/1352458515588581 [doi]
AB  - BACKGROUND: The association between Epstein-Barr virus (EBV) and multiple 
      sclerosis (MS) may involve intrathecal EBV-specific T-cell responses targeting 
      the virus or indirectly, autoantigens. OBJECTIVE: Compare the prevalence and 
      fine-specificity of EBV-specific T-cells in the cerebrospinal fluid (CSF) of 
      patients with MS (n = 12), clinically-isolated syndrome (CIS) (n = 17) and other 
      neurological diseases (OND) (n = 13). METHODS: Intrathecal EBV-specific T-cell 
      reactivity was assayed using CSF-derived T-cell lines (CSF-TCL) and autologous 
      EBV-transformed B-cells (autoBLCL) as antigen-presenting cells (APC). EBV 
      proteins recognized by autoBLCL-specific CD8 T-cells were identified using human 
      leukocyte antigen class I (HLA-I)-negative monkey cells as artificial APC, 
      co-transfected with 59 different EBV genes and the corresponding patient's HLA-I 
      alleles that were involved in autoBLCL T-cell reactivity. Reactivity towards the 
      MS-associated autoantigen alphaB-crystallin (CRYAB) was determined analogously. 
      RESULTS: CSF-TCL from CIS and MS patients had significantly higher frequencies of 
      autoBLCL-reactive CD4 T-cells, compared to the OND patients. CIS patients also 
      had significantly higher autoBLCL-reactive CD8 T cells, which correlated with 
      reactive CD4 T-cell frequencies. AutoBLCL-specific CD8 T-cell responses of four 
      CSF-TCL analyzed in detail were oligoclonal and directed to lytic EBV proteins, 
      but not CRYAB endogenously expressed by autoBLCL. CONCLUSIONS: Enhanced 
      intrathecal autoBLCL-specific T-cell reactivity, selectively directed towards 
      lytic EBV proteins in two CSF-TCL, suggested a localized T-cell response to EBV 
      in patients with MS. Our data warrant further characterization of the magnitude 
      and breadth of intrathecal EBV-specific T-cell responses in larger patient 
      cohorts.
CI  - (c) The Author(s), 2015.
FAU - van Nierop, Gijsbert P
AU  - van Nierop GP
AD  - Department of Neurology, Erasmus Medical Center, Rotterdam, the 
      Netherlands/Department of Viroscience, Erasmus Medical Center, Rotterdam, the 
      Netherlands.
FAU - Mautner, Josef
AU  - Mautner J
AD  - Helmholtz Zentrum Munchen and Technical University, Munich, Germany.
FAU - Mitterreiter, Johanna G
AU  - Mitterreiter JG
AD  - Department of Viroscience, Erasmus Medical Center, Rotterdam, the 
      Netherlands/Research Center for Emerging Infections and Zoonoses, University of 
      Veterinary Medicine, Hannover, Germany.
FAU - Hintzen, Rogier Q
AU  - Hintzen RQ
AD  - Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
FAU - Verjans, Georges M G M
AU  - Verjans GM
AD  - Department of Viroscience, Erasmus Medical Center, Rotterdam, the 
      Netherlands/Research Center for Emerging Infections and Zoonoses, University of 
      Veterinary Medicine, Hannover, Germany g.verjans@erasmusmc.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150603
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (Autoantigens)
RN  - 0 (CRYAB protein, human)
RN  - 0 (Viral Proteins)
RN  - 0 (alpha-Crystallin B Chain)
SB  - IM
MH  - Adult
MH  - Autoantigens/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epstein-Barr Virus Infections/*immunology
MH  - Female
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*cerebrospinal fluid/*immunology
MH  - Real-Time Polymerase Chain Reaction
MH  - Viral Proteins/*immunology
MH  - alpha-Crystallin B Chain/immunology
OTO - NOTNLM
OT  - Autoantibodies
OT  - Epstein-Barr virus
OT  - T-cells
OT  - cerebrospinal fluid
OT  - clinically-isolated syndrome
OT  - crystallin
OT  - disease control
OT  - herpesviridae
OT  - intrathecal space
OT  - lytic antigen
OT  - multiple sclerosis
OT  - target antigen
EDAT- 2015/06/05 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/06/05 06:00
PHST- 2014/10/30 00:00 [received]
PHST- 2015/05/01 00:00 [accepted]
PHST- 2015/06/05 06:00 [entrez]
PHST- 2015/06/05 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 1352458515588581 [pii]
AID - 10.1177/1352458515588581 [doi]
PST - ppublish
SO  - Mult Scler. 2016 Mar;22(3):279-91. doi: 10.1177/1352458515588581. Epub 2015 Jun 
      3.