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Peripheral Deletion of CD8 T Cells Requires p38 MAPK in Cross-Presenting Dendritic Cells
- Source :
- Journal of Immunology, Journal of Immunology, In press, ⟨10.4049/jimmunol.1700427⟩, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, In press, ⟨10.4049/jimmunol.1700427⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
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.
- Subjects :
- 0301 basic medicine
[SDV.IMM] Life Sciences [q-bio]/Immunology
T cell
Immunology
Peripheral tolerance
CD28
Biology
Natural killer T cell
Clonal deletion
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
medicine
Immunology and Allergy
Cytotoxic T cell
[SDV.IMM]Life Sciences [q-bio]/Immunology
IL-2 receptor
Antigen-presenting cell
ComputingMilieux_MISCELLANEOUS
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 00221767 and 15506606
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology, Journal of Immunology, In press, ⟨10.4049/jimmunol.1700427⟩, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, In press, ⟨10.4049/jimmunol.1700427⟩
- Accession number :
- edsair.doi.dedup.....23b1524f62be52fb5b57577125e32679
- Full Text :
- https://doi.org/10.4049/jimmunol.1700427