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PMID: 15184500 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes.

The Journal of experimental medicine ·Vol. 199 ·No. 11 ·2004-06-07 ·Pages 1467-77

Tarbell KV, Yamazaki S, Olson K, Toy P, Steinman RM

Abstract

In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet beta cells. To silence autoimmunity, we used dendritic cells (DCs) from NOD mice to expand CD25+ CD4+ suppressor T cells from BDC2.5 mice, which are specific for a single islet autoantigen. The expanded T cells were more suppressive in vitro than their freshly isolated counterparts, indicating that DCs from autoimmune mice can increase the number and function of antigen-specific, CD25+ CD4+ regulatory T cells. Importantly, only 5,000 expanded CD25+ CD4+ BDC2.5 T cells could block autoimmunity caused by diabetogenic T cells in NOD mice, whereas 10(5) polyclonal, CD25+ CD4+ T cells from NOD mice were inactive. When islets were examined in treated mice, insulitis development was blocked at early (3 wk) but not later (11 wk) time points. The expanded CD25+ CD4+ BDC2.5 T cells were effective even if administered 14 d after the diabetogenic T cells. Our data indicate that DCs can generate CD25+ CD4+ T cells that suppress autoimmune disease in vivo. This might be harnessed as a new avenue for immunotherapy, especially because CD25+ CD4+ regulatory cells responsive to a single autoantigen can inhibit diabetes mediated by reactivity to multiple antigens.

MeSH Terms
Animals Antigen Presentation Autoantigens/immunology CD4 Antigens/analysis Dendritic Cells/physiology Diabetes Mellitus, Type 1/prevention & control Female Immunophenotyping Islets of Langerhans/pathology Male Mice Mice, Inbred NOD Receptors, Interleukin-2/analysis T-Lymphocytes, Regulatory/immunology
Chemicals
Autoantigens CD4 Antigens Receptors, Interleukin-2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Tarbell Kristin V
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Yamazaki Sayuri
Olson Kara
Toy Priscilla
Steinman Ralph M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20040180
Published
2004-06-07
Pages
1467-77
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2211787
Subset
IM
Grants
NIAID NIH HHS · P01 AI051573 · United States
NIAID NIH HHS · AI 51573-02 · United States
External Links
PubMed source DOI: 10.1084/jem.20040180 PMC Full Text View journal details
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