Down-modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitis

Chunhe Wang, Yuexin Li, Thomas M. Proctor, Arthur Vandenbark, Halina Offner

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32 Citations (Scopus)

Abstract

The regulatory role of programmed death 1 (PD-1) was investigated in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Typical EAE could be induced by immunization without pertussis toxin (PTX) in PD-1-null but not in wild-type (WT) mice. However, both strains developed a similar EAE phenotype when immunized with PTX or by adoptive transfer of pathogenic T cells. In WT mice that did not develop EAE after immunization without PTX, the frequency of CD4+FoxP3 + Treg cells was boosted in the periphery but not in the thymus. This increase in Treg frequency was abrogated by PD-1 deficiency or inclusion of PTX. In addition, PD-1 expression was critical to in vitro conversion of naïve myelin-specific CD4 T cells into Treg cells and was directly related to Treg suppressive activity. Finally, PD-1 was markedly down-modulated in the periphery of WT mice after administration of PTX. Therefore, down-modulation of PD-1 in Treg cells may abrogate Treg-mediated immune suppression, permitting the activation of myelin-reactive T cells and induction of EAE.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalJournal of Neuroscience Research
Volume88
Issue number1
DOIs
StatePublished - Jan 2010

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Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
Pertussis Toxin
Myelin Sheath
T-Lymphocytes
Immunization
Adoptive Transfer
Thymus Gland
Multiple Sclerosis
Animal Models
Phenotype

Keywords

  • Experimental autoimmune encephalomyelitis
  • Multiple sclerosis
  • Pertussis toxin
  • Programmed death 1
  • Regulatory T cells

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Down-modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitis. / Wang, Chunhe; Li, Yuexin; Proctor, Thomas M.; Vandenbark, Arthur; Offner, Halina.

In: Journal of Neuroscience Research, Vol. 88, No. 1, 01.2010, p. 7-15.

Research output: Contribution to journalArticle

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