Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells.
Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide-matured DC and CD4(pos) T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4(pos) T cell activation, we observed that a significant fraction of CD4(pos) T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL-2, IFN-gamma, IL-10 and TGF-beta. Furthermore, CD4(pos) T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third-party stimulators were spared. The generation of CD4(pos) T cells with regulatory function by autologous stimulation did not require the presence of natural CD4(pos)CD25(pos) regulatory T cells. In addition, the acquisition of regulatory function by CD4(pos)CD25(neg) T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.|present address: INSERM-03 44, Université de Nice-Sophia Antipolis, IPMC, Valbonne, France.
Valérie
V
Verhasselt
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Olivier
O
Vosters
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Claire
C
Beuneu
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Charles
C
Nicaise
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Patrick
P
Stordeur
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Michel
M
Goldman
D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D051858:Forkhead Transcription Factors; D006133:Growth Substances / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2