Apoptotic cell capture by DCs induces unexpectedly robust autologous CD4+ T-cell responses.
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.
Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; University Paris Descartes, Paris, France.
Michael
M
Valente
Camille
C
Baey
Pauline
P
Louche
Charles-Antoine
CA
Dutertre
Lene
L
Vimeux
Concepción
C
Marañón
Anne
A
Hosmalin
Vincent
V
Feuillet
D017951:Antigen Presentation; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D058504:Th17 Cells / Q000276:immunology
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D008070:Lipopolysaccharides
Apoptotic cells; CD4+ T-cell responses; Dendritic cells