Down‐modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitis
- 29 July 2009
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 88 (1), 7-15
- https://doi.org/10.1002/jnr.22181
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.Keywords
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