Peripheral Deletion of CD8 T Cells Requires p38 MAPK in Cross-Presenting Dendritic Cells.
J Immunol
; 199(8): 2713-2720, 2017 10 15.
Article
em En
| MEDLINE
| ID: mdl-28864471
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Deleção Clonal
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Linfócitos T CD8-Positivos
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Proteínas Quinases p38 Ativadas por Mitógeno
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Tolerância Periférica
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article