Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells.
Coupling of ovalbumin (OVA) to anti-DEC-205 monoclonal antibody (mAb) (alphaDEC) induced the proliferation of OVA-specific T cells in vivo. Expansion was short-lived, caused by dendritic cells (DCs), and rendered T cells anergic thereafter. Phenotypic analysis revealed the induction of CD25+/CTLA-4+ T cells suppressing proliferation and interleukin-2 (IL-2) production of effector CD4+ T cells. The findings were supported by 2 disease models: (1) CD4+ T-cell-mediated hypersensitivity reactions were suppressed by the injection of alphaDEC-OVA and (2) the application of hapten-coupled alphaDEC-205 reduced CD8+ T-cell-mediated allergic reactions. Thus, targeting of antigens to immature DCs through alphaDEC antibodies led to the induction of regulatory T cells, providing the basis for novel strategies to induce regulatory T cells in vivo.
Mahnke
Karsten
K
Department of Dermatology, University of Mainz, Germany. mahnke@hautklinik.klinik.uni-mainz.de
Qian
Yingjie
Y
Knop
Jürgen
J
Enk
Alexander H
AH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D006241:Haptens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D010047:Ovalbumin