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 language | English (US) |
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Pages (from-to) | 7-15 |
Number of pages | 9 |
Journal | Journal of Neuroscience Research |
Volume | 88 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2010 |
Keywords
- Experimental autoimmune encephalomyelitis
- Multiple sclerosis
- Pertussis toxin
- Programmed death 1
- Regulatory T cells
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience