PMID- 20661655
OWN - NLM
STAT- MEDLINE
DCOM- 20101123
LR  - 20211020
IS  - 1557-1904 (Electronic)
IS  - 1557-1890 (Print)
IS  - 1557-1890 (Linking)
VI  - 5
IP  - 3
DP  - 2010 Sep
TI  - Mechanism of neuroinflammation: enhanced cytotoxicity and IL-17 production via 
      CD46 binding.
PG  - 469-78
LID - 10.1007/s11481-010-9232-9 [doi]
AB  - The membrane co-factor protein CD46 is the cellular receptor for a number of 
      pathogens including the human herpesvirus 6 (HHV-6). In addition to its function 
      as an inhibitory complement receptor, engagement of CD46 in the context of T-cell 
      receptor (TCR) signaling influences T-cell activation. Simultaneous cross-linking 
      of the CD3/CD46 molecules led to differentiation of a unique population of CD4+ 
      T-cell subset characterized by enhanced expressions of IFN-gamma, IL-10, granzyme 
      B, adhesion molecule MAdCAM-1 (alpha-4-beta-7), surface-bound cytokine LIGHT, and 
      chemokine receptor CCR9. Multiple sclerosis is a chronic inflammatory 
      neurodegenerative disorder of the central nervous system (CNS) with unknown 
      etiology. The HHV-6 is a candidate pathogen in MS and uses the CD46 molecule as 
      its receptor. We hypothesize that binding of the HHV-6 glycoprotein to CD46 may 
      trigger a pro-inflammatory response that could contribute to CNS tissue damage. 
      To address this question, we examined immunological parameters such as 
      proliferation, cytokine production and cytotoxic functions in CD4+ T cells of 
      healthy individuals and MS patients following CD3/CD46 co-engagement by using 
      anti-CD3 and anti-CD46 monoclonal antibodies as surrogates to mimic T-cell 
      receptor and CD46 signaling. Our results demonstrated that CD3/CD46 cross-linking 
      induced expression of IL-1beta and IL-17A in multiple sclerosis patient T cells. 
      Additionally, increase in transient surface expression of lysosomal associated 
      protein CD107a suggested enhanced CD4+ T-cell cytotoxic functions following 
      CD3/CD46 co-stimulation. Collectively, this study demonstrated evidence to 
      suggest a potential mechanism of virus-induced neuroinflammation that may be 
      involved in MS disease pathogenesis.
FAU - Yao, Karen
AU  - Yao K
AD  - Viral Immunology Section, NINDS, NIH, Bethesda, MD 20892, USA.
FAU - Graham, Jhanelle
AU  - Graham J
FAU - Akahata, Yoshimi
AU  - Akahata Y
FAU - Oh, Unsong
AU  - Oh U
FAU - Jacobson, Steven
AU  - Jacobson S
LA  - eng
GR  - Z01 NS002817-18/ImNIH/Intramural NIH HHS/United States
GR  - Z01 NS002817-19/ImNIH/Intramural NIH HHS/United States
GR  - Z01 NS003040-01/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20100727
PL  - United States
TA  - J Neuroimmune Pharmacol
JT  - Journal of neuroimmune pharmacology : the official journal of the Society on 
      NeuroImmune Pharmacology
JID - 101256586
RN  - 0 (Interleukin-17)
RN  - 0 (Membrane Cofactor Protein)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/immunology/physiology
MH  - Cells, Cultured
MH  - Herpesvirus 6, Human/immunology/physiology
MH  - Humans
MH  - Interleukin-17/biosynthesis/immunology/*physiology
MH  - Lymphocyte Activation/immunology
MH  - Membrane Cofactor Protein/immunology/*physiology
MH  - Multiple Sclerosis/immunology/physiopathology
MH  - Multiple Sclerosis, Relapsing-Remitting/immunology/physiopathology
MH  - Neurogenic Inflammation/*immunology/physiopathology
MH  - Roseolovirus Infections/immunology/metabolism/physiopathology
MH  - T-Lymphocytes/immunology/physiology
PMC - PMC4758197
MID - NIHMS757864
EDAT- 2010/07/28 06:00
MHDA- 2010/12/14 06:00
PMCR- 2016/02/18
CRDT- 2010/07/28 06:00
PHST- 2009/11/24 00:00 [received]
PHST- 2010/06/28 00:00 [accepted]
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2016/02/18 00:00 [pmc-release]
AID - 10.1007/s11481-010-9232-9 [doi]
PST - ppublish
SO  - J Neuroimmune Pharmacol. 2010 Sep;5(3):469-78. doi: 10.1007/s11481-010-9232-9. 
      Epub 2010 Jul 27.