CD40 Mediates Maturation of Thymic Dendritic Cells Driven by Self-Reactive CD4+ Thymocytes and Supports Development of Natural Regulatory T Cells.
J Immunol
; 200(4): 1399-1412, 2018 02 15.
Article
em En
| MEDLINE
| ID: mdl-29321275
ABSTRACT
Thymic dendritic cells (tDCs) play an important role in central tolerance by eliminating self-reactive thymocytes or differentiating them to regulatory T (Treg) cells. However, the molecular and cellular mechanisms underlying these functions are not completely understood. We found that mouse tDCs undergo maturation following cognate interaction with self-reactive CD4+ thymocytes and that this maturation is dependent on CD40 signaling. Ablation of CD40 expression in tDCs resulted in a significant reduction in the number of Treg cells in association with a significant reduction in the number of mature tDCs. In addition, CD40-deficient DCs failed to fully mature upon cognate interaction with CD4+ thymocytes in vitro and failed to differentiate them into Treg cells to a sufficient number. These findings suggest that tDCs mature and potentiate Treg cell development in feedback response to self-reactive CD4+ thymocytes.
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Base de dados:
MEDLINE
Assunto principal:
Timo
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Células Dendríticas
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Tolerância a Antígenos Próprios
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Antígenos CD40
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Timócitos
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article