Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 199, Issue 11, Pages 1467-1477Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20040180
Keywords
insulin-dependent diabetes mellitus; dendritic cells; CD25(+) CD4(+) regulatory T cells; BDC2.5; autoimmunity
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Funding
- NIAID NIH HHS [P01 AI051573, AI 51573-02] Funding Source: Medline
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In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet P 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.
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