Apoptotic cell capture by DCs induces unexpectedly robust autologous CD4(+) T-cell responses

作者:Valente Michael; Baey Camille; Louche Pauline; Dutertre Charles Antoine; Vimeux Lene; Maranon Concepcion; Hosmalin Anne; Feuillet Vincent*
来源:European Journal of Immunology, 2014, 44(8): 2274-2286.
DOI:10.1002/eji.201344191

摘要

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.

  • 出版日期2014-8