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Intrinsic and induced regulation of the age-associated onset of spontaneous experimental autoimmune encephalomyelitis.

Publication ,  Journal Article
Zhang, H; Podojil, JR; Luo, X; Miller, SD
Published in: J Immunol
October 1, 2008

Multiple sclerosis is characterized by perivascular CNS infiltration of myelin-specific CD4(+) T cells and activated mononuclear cells. TCR transgenic mice on the SJL background specific for proteolipid protein (PLP)(139-151) develop a high incidence of spontaneous experimental autoimmune encephalomyelitis (sEAE). We examined the intrinsic mechanisms regulating onset and severity of sEAE. CD4(+) T cells isolated from the cervical lymph nodes, but not spleens, of diseased 5B6 transgenic mice are hyperactivated when compared with age-matched healthy mice and produce both IFN-gamma and IL-17, indicating that the cervical lymph node is the initial peripheral activation site. The age-associated development of sEAE correlates with a decline in both the functional capacity of natural regulatory T cells (nTregs) and in PLP(139-151)-induced IL-10 production and a concomitant increase in IL-17 production. Anti-CD25-induced inactivation of nTregs increased the incidence and severity of sEAE. Conversely, induction of peripheral tolerance via the i.v. injection of PLP(139-151)-pulsed, ethylcarbodiimide-fixed APCs (PLP(139-151)-SP) inhibited the development of clinical disease concomitant with increased production of IL-10 and conversion of Foxp3(+) Tregs from CD4(+)CD25(-) progenitors. These data indicate that heterogeneous populations of Tregs regulate onset of sEAE, and that induction of peripheral tolerance can be exploited to prevent/treat spontaneous autoimmune disease.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 1, 2008

Volume

181

Issue

7

Start / End Page

4638 / 4647

Location

United States

Related Subject Headings

  • Time Factors
  • Severity of Illness Index
  • Peptide Fragments
  • Myelin Proteolipid Protein
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred Strains
  • Mice, Inbred C57BL
  • Mice
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, H., Podojil, J. R., Luo, X., & Miller, S. D. (2008). Intrinsic and induced regulation of the age-associated onset of spontaneous experimental autoimmune encephalomyelitis. J Immunol, 181(7), 4638–4647. https://doi.org/10.4049/jimmunol.181.7.4638

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 1, 2008

Volume

181

Issue

7

Start / End Page

4638 / 4647

Location

United States

Related Subject Headings

  • Time Factors
  • Severity of Illness Index
  • Peptide Fragments
  • Myelin Proteolipid Protein
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred Strains
  • Mice, Inbred C57BL
  • Mice
  • Immunology