PMID- 24227784
OWN - NLM
STAT- MEDLINE
DCOM- 20140218
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 191
IP  - 12
DP  - 2013 Dec 15
TI  - The kinetics of myelin antigen uptake by myeloid cells in the central nervous 
      system during experimental autoimmune encephalomyelitis.
PG  - 5848-57
LID - 10.4049/jimmunol.1300771 [doi]
AB  - Induction of experimental autoimmune encephalomyelitis (EAE) in susceptible 
      animals requires reactivation of encephalitogenic CD4(+) T cells by APCs in the 
      CNS. However, it has remained unresolved from where APCs in the CNS acquire 
      myelin Ag for T cell activation and under which conditions, that is, whether only 
      during EAE or also in the naive CNS. In this study, we investigated the kinetics 
      of myelin Ag uptake by CNS APCs during EAE and in the naive CNS. Our results show 
      that during EAE CX3CR1(+)CD11b(+) microglia were the first APCs in the CNS to 
      contain myelin Ag upon induction of disease, albeit in very small numbers. 
      Dendritic cells (DCs) arrived in the CNS in sizable numbers significantly later 
      (day 5 postimmunization), without detectable myelin Ag, but acquired it by day 7 
      postimmunization. Furthermore, a sharp increase in neuroantigen-containing DCs 
      coincided with the onset of EAE symptoms. Importantly, in naive mice a low but 
      consistent number of microglia contained myelin Ag, suggesting release by 
      oligodendrocytes under steady state conditions. Although microglia isolated from 
      naive brain and spinal cord did not elicit a strong CD4(+) T cell response in 
      vitro, myelin Ag-containing microglia may still play a local role in modulating 
      encephalitogenic CD4(+) T cell responses in early EAE prior to the arrival of 
      other professional APCs, such as DCs. Finally, newly arriving DCs in the CNS not 
      yet loaded with myelin Ag before the onset of EAE may be a potential therapeutic 
      target.
FAU - Sosa, Rebecca A
AU  - Sosa RA
AD  - Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249.
FAU - Murphey, Cathi
AU  - Murphey C
FAU - Ji, Niannian
AU  - Ji N
FAU - Cardona, Astrid E
AU  - Cardona AE
FAU - Forsthuber, Thomas G
AU  - Forsthuber TG
LA  - eng
GR  - NS-52177/NS/NINDS NIH HHS/United States
GR  - G12MD007591/MD/NIMHD NIH HHS/United States
GR  - SC1GM095426/GM/NIGMS NIH HHS/United States
GR  - SC1 GM095426/GM/NIGMS NIH HHS/United States
GR  - R01 NS052177/NS/NINDS NIH HHS/United States
GR  - G12 MD007591/MD/NIMHD NIH HHS/United States
GR  - G12 RR013646/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131113
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens)
RN  - 0 (Autoantibodies)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Myelin Proteolipid Protein)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptide Fragments)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
RN  - 0 (myelin proteolipid protein (139-151))
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - EC 2.4.2.31 (Pertussis Toxin)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens/immunology/*metabolism
MH  - Autoantibodies/biosynthesis/immunology
MH  - Brain/immunology/*metabolism
MH  - Cell Movement
MH  - Dendritic Cells/immunology/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/*metabolism
MH  - Female
MH  - Freund's Adjuvant
MH  - Imaging, Three-Dimensional
MH  - Immunization
MH  - Injections, Intraperitoneal
MH  - Injections, Subcutaneous
MH  - Lymphocyte Activation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Neurologic Mutants
MH  - Mice, Transgenic
MH  - Microglia/metabolism
MH  - Microscopy, Confocal
MH  - Myelin Basic Protein/analysis/immunology
MH  - Myelin Proteolipid Protein/immunology/*pharmacokinetics
MH  - Myelin-Oligodendrocyte Glycoprotein/immunology/*pharmacokinetics
MH  - Myeloid Cells/*metabolism
MH  - Peptide Fragments/immunology/*pharmacokinetics
MH  - Pertussis Toxin
MH  - Spinal Cord/immunology/*metabolism
PMC - PMC3891847
MID - NIHMS529733
EDAT- 2013/11/15 06:00
MHDA- 2014/02/19 06:00
PMCR- 2014/12/15
CRDT- 2013/11/15 06:00
PHST- 2013/11/15 06:00 [entrez]
PHST- 2013/11/15 06:00 [pubmed]
PHST- 2014/02/19 06:00 [medline]
PHST- 2014/12/15 00:00 [pmc-release]
AID - jimmunol.1300771 [pii]
AID - 10.4049/jimmunol.1300771 [doi]
PST - ppublish
SO  - J Immunol. 2013 Dec 15;191(12):5848-57. doi: 10.4049/jimmunol.1300771. Epub 2013 
      Nov 13.