Peripheral Deletion of CD8 T Cells Requires p38 MAPK in Cross-Presenting Dendritic Cells.

Détails

ID Serval
serval:BIB_53F45409F322
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Peripheral Deletion of CD8 T Cells Requires p38 MAPK in Cross-Presenting Dendritic Cells.
Périodique
Journal of immunology
Auteur(s)
Smith T., Lin X., Mello M., Marquardt K., Cheung J., Lu B., Sherman L.A., Verdeil G.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
15/10/2017
Peer-reviewed
Oui
Volume
199
Numéro
8
Pages
2713-2720
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Peripheral tolerance mechanisms exist to prevent autoimmune destruction by self-reactive T cells that escape thymic deletion. Dominant tolerance imposed by CD4(+)Foxp3(+) T regulatory cells can actively control autoaggressive T cell responses. Tolerance mechanisms that act endogenous to the T cell also exist. These mechanisms include T cell inactivation (anergy) and deletion. A major difference between anergic T cells and T cells undergoing peripheral deletion is the capacity of the latter to still signal through MAPKs upon TCR stimulation, suggesting these signals may be required for T deletion. In this study, we used several different models of CD8 T cell deletion to investigate the contribution of MAPK activation. Using chemical inhibitors, we established that inhibition of p38, but not ERK or JNK, rescue T cells from undergoing peripheral deletion both in vitro and in vivo. Using T cell-specific murine lines genetically altered in expression of p38α, and mice in which p38α was deleted only in CD11c-expressing cells, we surprisingly found that CD8 T cell-intrinsic p38α activation was not responsible for increased survival, but rather that inhibition of p38α in the Ag-presenting dendritic cells prevented CD8 T cell deletion.

Mots-clé
Animals, Antigens, CD11c/metabolism, CD8-Positive T-Lymphocytes/physiology, Cell Line, Clonal Deletion, Cross-Priming, Dendritic Cells/immunology, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Peripheral Tolerance, Receptors, Antigen, T-Cell/genetics, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, p38 Mitogen-Activated Protein Kinases/genetics, p38 Mitogen-Activated Protein Kinases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/09/2017 13:51
Dernière modification de la notice
20/08/2019 15:08
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