Abstract
CD4+CD25+ regulatory T cells are essential in the protection from organ-specific autoimmune diseases. In the pancreas, they inhibit actions of autoreactive T cells and thereby prevent diabetes progression. The signals that control the generation, the maintenance, or the expansion of regulatory T cell pool in vivo remain poorly understood. Here we show that a transient pulse of transforming growth factor beta (TGF-beta) in the islets during the priming phase of diabetes is sufficient to inhibit disease onset by promoting the expansion of intraislet CD4+CD25+ T cell pool. Approximately 40-50% of intraislet CD4+ T cells expressed the CD25 marker and exhibited characteristics of regulatory T cells including small size, high level of intracellular CTLA-4, expression of Foxp3, and transfer of protection against diabetes. Results from in vivo incorporation of BrdUrd revealed that the generation of a high frequency of regulatory T cells in the islets is due to in situ expansion upon TGF-beta expression. Thus, these findings demonstrate a previously uncharacterized mechanism by which TGF-beta inhibits autoimmune diseases via regulation of the size of the CD4+CD25+ regulatory T cell pool in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 4572-7 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 101 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 2004 |
Keywords
- Adoptive Transfer
- Animals
- Antigens, CD4
- Base Sequence
- CD4-Positive T-Lymphocytes
- DNA Primers
- DNA-Binding Proteins
- Diabetes Mellitus
- Doxycycline
- Forkhead Transcription Factors
- Gene Expression Regulation
- Hypoxanthine Phosphoribosyltransferase
- Islets of Langerhans
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Receptors, Interleukin-2
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes
- Transforming Growth Factor beta