| Dendritic cells with TGF-beta1 differentiate naive CD4+CD25- T cells into islet-protective Foxp3+ regulatory T cells. | |
| | |
MedLine Citation:
|
PMID: 17307871 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
CD4(+)CD25(+)Foxp3(+) regulatory T cells (T regs) are important for preventing autoimmune diabetes and are either thymic-derived (natural) or differentiated in the periphery outside the thymus (induced). Here we show that beta-cell peptide-pulsed dendritic cells (DCs) from nonobese diabetic (NOD) mice can effectively induce CD4(+)CD25(+)Foxp3(+) T cells from naïve islet-specific CD4(+)CD25(-) T cells in the presence of TGF-beta1. These induced, antigen-specific T regs maintain high levels of clonotype-specific T cell receptor expression and exert islet-specific suppression in vitro. When cotransferred with diabetogenic cells into NOD scid recipients, T regs induced with DCs and TGF-beta1 prevent the development of diabetes. Furthermore, in overtly NOD mice, these cells are able to significantly protect syngeneic islet grafts from established destructive autoimmunity. These results indicate a role for DCs in the induction of antigen-specific CD4(+)CD25(+)Foxp3(+) T cells that can inhibit fully developed autoimmunity in a nonlymphopoenic host, providing an important potential strategy for immunotherapy in patients with autoimmune diabetes. |
| | |
Authors:
|
Xunrong Luo; Kristin V Tarbell; Hua Yang; Kathryn Pothoven; Samantha L Bailey; Ruchuang Ding; Ralph M Steinman; Manikkam Suthanthiran |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-02-16 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2007 Feb |
Date Detail:
|
Created Date: 2007-03-15 Completed Date: 2007-04-12 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 2821-6 Citation Subset: IM |
Affiliation:
|
Division of Nephrology, Department of Medicine, and the Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antigens, CD11c / immunology Antigens, CD4 / immunology* Cell Differentiation / drug effects* Cell Proliferation / drug effects Dendritic Cells / drug effects, immunology* Diabetes Mellitus, Type 1 / immunology Female Forkhead Transcription Factors / immunology* Interleukin-2 Receptor alpha Subunit / immunology* Islets of Langerhans / cytology, drug effects, immunology Islets of Langerhans Transplantation Mice Mice, Inbred NOD Peptides Spleen / cytology, drug effects T-Lymphocytes, Regulatory / cytology, drug effects*, immunology, transplantation Transforming Growth Factor beta1 / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
|
1K08 DK 070029-01/DK/NIDDK NIH HHS; 5K01 DK 071586-02/DK/NIDDK NIH HHS; AI 51573/AI/NIAID NIH HHS; R21 DK 60186/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, CD11c; 0/Antigens, CD4; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Interleukin-2 Receptor alpha Subunit; 0/Peptides; 0/Transforming Growth Factor beta1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibiti...
Next Document: Genome-wide transcription map of an archaeal cell cycle.