Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 44, Issue 8, Pages 2274-2286Publisher
WILEY
DOI: 10.1002/eji.201344191
Keywords
Apoptotic cells; CD4(+) T-cell responses; Dendritic cells
Categories
Funding
- INSERM
- CNRS-AP-HP-CHU Cochin collaboration
- ANRS
- Sidaction
- French Government's Investissement d'Avenir program
- Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
- Universite Paris Descartes
- Universite Paris Diderot
- FRM
- Ligue de Recherche Contre le Cancer
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Apoptotic cells represent an important source of self-antigens and their engulfment by dendritic cells (DCs) is usually considered to be related to tolerance induction. We report here an unexpectedly high level of human CD4(+) T-cell proliferation induced by autologous DCs loaded with autologous apoptotic cells, due to the activation of more than 10% of naive CD4(+) T cells. This proliferation is not due to an increase in the costimulatory capacity of DCs, but is dependent on apoptotic cell-associated material processed through an endo-lysosomal pathway and presented on DC MHC class II molecules. Autologous CD4(+) T cells stimulated with apoptotic cell-loaded DCs exhibit suppressive capacities. However, in the presence of bacterial lipopolysaccharide, apoptotic cell-loaded DCs induce the generation of IL-17-producing cells. Thus, apoptotic cell engulfment by DCs may lead to increased autologous responses, initially generating CD4(+) T cells with suppressive capacities able to differentiate into Th17 cells in the presence of a bacterial danger signal such as LPS.
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