Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway.
Targeted immune regulation can be achieved by use of tissue-specific T cells and offers the potential for organ-specific suppression of destructive autoimmune processes. Here, we report the generation and characterization of insulin B chain-specific "autoreactive" CD4+ regulatory T cells that locally suppress diabetogenic T cell responses against an unrelated self-antigen (viral transgene) in a virus-induced model for type 1 diabetes. Interleukin 4 (IL-4) is essential for prevention of diabetes since regulatory T cells cannot be induced in the absence of IL-4 or stat6 (IL-4 signaling pathway). Our observations demonstrate that autoreactive regulatory T cells can suppress autoreactive destructive T cell activity of differential antigenic specificity locally in the pancreatic draining lymph node, probably via cytokine-mediated modulation of antigen-presenting cells.
Homann
D
D
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Holz
A
A
Bot
A
A
Coon
B
B
Wolfe
T
T
Petersen
J
J
Dyrberg
T P
TP
Grusby
M J
MJ
von Herrath
M G
MG
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007328:Insulin / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D010179:Pancreas / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D050800:STAT6 Transcription Factor; D013552:Swine; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D007328:Insulin; D009698:Nucleoproteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014764:Viral Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma