PMID- 26893156
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20181113
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 13
DP  - 2016 Feb 18
TI  - Protection from experimental autoimmune encephalomyelitis by polyclonal IgG 
      requires adjuvant-induced inflammation.
PG  - 42
LID - 10.1186/s12974-016-0506-x [doi]
LID - 42
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) proved to be an efficient 
      anti-inflammatory treatment for a growing number of neuroinflammatory diseases 
      and protects against the development of experimental autoimmune encephalomyelitis 
      (EAE), a widely used animal model for multiple sclerosis (MS). METHODS: The 
      clinical efficacy of IVIG and IVIG-derived F(ab')2 fragments, generated using the 
      streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active 
      immunization and by adoptive transfer of myelin-specific T cells. Frequency, 
      phenotype, and functional characteristics of T cell subsets and myeloid cells 
      were determined by flow cytometry. Antibody binding to microbial antigen and 
      cytokine production by innate immune cells was assessed by ELISA. RESULTS: We 
      report that the protective effect of IVIG is lost in the adoptive transfer model 
      of EAE and requires prophylactic administration during disease induction. 
      IVIG-derived Fc fragments are not required for protection against EAE, since 
      administration of F(ab')2 fragments fully recapitulated the clinical efficacy of 
      IVIG. F(ab')2-treated mice showed a substantial decrease in splenic effector T 
      cell expansion and cytokine production (GM-CSF, IFN-gamma, IL-17A) 9 days after 
      immunization. Inhibition of effector T cell responses was not associated with an 
      increase in total numbers of Tregs but with decreased activation of innate 
      myeloid cells such as neutrophils, monocytes, and dendritic cells. 
      Therapeutically effective IVIG-derived F(ab')2 fragments inhibited 
      adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 
      production and recognized mycobacterial antigens contained in Freund's complete 
      adjuvant which is required for induction of active EAE. CONCLUSIONS: Our data 
      indicate that F(ab')2-mediated neutralization of adjuvant contributes to the 
      therapeutic efficacy of anti-inflammatory IgG. These findings might partly 
      explain the discrepancy of IVIG efficacy in EAE and MS.
FAU - Quast, Isaak
AU  - Quast I
AD  - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University 
      of Zurich, Zurich, Switzerland. isaak.quast@uzh.ch.
FAU - Keller, Christian W
AU  - Keller CW
AD  - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University 
      of Zurich, Zurich, Switzerland. keller@immunology.uzh.ch.
FAU - Weber, Patrick
AU  - Weber P
AD  - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University 
      of Zurich, Zurich, Switzerland. weber@immunology.uzh.ch.
FAU - Schneider, Christoph
AU  - Schneider C
AD  - Institute of Pharmacology, University of Bern, Bern, Switzerland. 
      christoph.schneider@pki.unibe.ch.
FAU - von Gunten, Stephan
AU  - von Gunten S
AD  - Institute of Pharmacology, University of Bern, Bern, Switzerland. 
      stephan.vongunten@pki.unibe.ch.
FAU - Lunemann, Jan D
AU  - Lunemann JD
AD  - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University 
      of Zurich, Zurich, Switzerland. jan.luenemann@uzh.ch.
LA  - eng
PT  - Journal Article
DEP - 20160218
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Antigens, CD)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Immunologic Factors)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens, CD/metabolism
MH  - Disease Models, Animal
MH  - Encephalomyelitis, Autoimmune, Experimental/chemically induced/*drug 
      therapy/genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Freund's Adjuvant/toxicity
MH  - Immunoglobulins, Intravenous/*therapeutic use
MH  - Immunologic Factors/*therapeutic use
MH  - Leukocytes/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myelin-Oligodendrocyte Glycoprotein/toxicity
MH  - Peptide Fragments/toxicity
MH  - Receptors, Antigen, T-Cell/genetics
MH  - Spleen/pathology
MH  - Time Factors
PMC - PMC4758141
EDAT- 2016/02/20 06:00
MHDA- 2016/10/07 06:00
PMCR- 2016/02/18
CRDT- 2016/02/20 06:00
PHST- 2015/11/23 00:00 [received]
PHST- 2016/02/08 00:00 [accepted]
PHST- 2016/02/20 06:00 [entrez]
PHST- 2016/02/20 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
PHST- 2016/02/18 00:00 [pmc-release]
AID - 10.1186/s12974-016-0506-x [pii]
AID - 506 [pii]
AID - 10.1186/s12974-016-0506-x [doi]
PST - epublish
SO  - J Neuroinflammation. 2016 Feb 18;13:42. doi: 10.1186/s12974-016-0506-x.