Therapeutic potential of self-antigen-specific CD4+ CD25+ regulatory T cells selected in vitro from a polyclonal repertoire.
CD4+ CD25+ regulatory T cells (Treg) play a major role in the prevention of autoimmune diseases. Converging evidence indicates that Treg specific for self-antigens expressed by target tissues have a greater therapeutic potential than polyclonal Treg. Therefore, the selective expansion of rare self-antigen-specific T(reg) naturally present in a polyclonal repertoire of Treg is of major importance. In this work, we investigated the potential of different dendritic cell (DC) subsets to expand antigen-specific Treg in mice. The in vitro selective expansion of rare islet-specific Treg from polyclonal Treg could only be achieved efficiently by stimulation with CD8+ splenic DC presenting islet antigens. These islet-specific Treg exerted potent bystander suppression on diabetogenic T cells and prevented type 1 diabetes. This approach opens new perspectives for cell therapy of autoimmune diseases.
Fisson
Sylvain
S
CNRS UMR 7087 and Université Pierre et Marie Curie, CERVI, Hôpital de la Pitié-Salpêtrière, Paris, France.
Djelti
Fathia
F
Trenado
Aurélie
A
Billiard
Fabienne
F
Liblau
Roland
R
Klatzmann
David
D
Cohen
José L
JL
Salomon
Benoît L
BL
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001324:Autoantigens; D015704:CD4 Antigens; D015375:Receptors, Interleukin-2