In Vivo Control of Diabetogenic T-Cells by Regulatory CD4 super(+)CD25 super(+) T-Cells Expressing Foxp3

To understand the ability of regulatory T-cells to control diabetes development in clinically relevant situations, we established a new model of accelerated diabetes in young DP-BB rats by transferring purified T-cells from DR-BB rats made acutely diabetic. Transfer of 3, 5, 10, or 23 million pure i...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Diabetes (New York, N.Y.) N.Y.), 2005-04, Vol.54 (4), p.1040-1047
Hauptverfasser: Lundsgaard, Dorthe, Holm, Thomas Lindebo, Hornum, Lars, Markholst, Helle
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:To understand the ability of regulatory T-cells to control diabetes development in clinically relevant situations, we established a new model of accelerated diabetes in young DP-BB rats by transferring purified T-cells from DR-BB rats made acutely diabetic. Transfer of 3, 5, 10, or 23 million pure in vitro-activated T-cells accelerated diabetes onset in >90% of the recipients, with the degree of acceleration being dosage dependent. Cotransfer of unfractionated leukocytes from healthy donors prevented diabetes. Full protection was achieved when protective cells were transferred 3-4 days before diabetogenic cells, whereas transfer 2 days before conferred only partial protection. Protection resided in the CD4 super(+) fraction, as purified CD4 super(+) T-cells prevented the accelerated diabetes. When CD25 super(+) cells were depleted from these cells before they were transferred, their ability to prevent diabetes was impaired. In contrast, two million CD4 super(+)CD25 super(+) cells (expressing Foxp3) prevented the accelerated diabetes when transferred both before and simultaneously with the diabetogenic T-cells. In addition, 2 million CD4 super(+)CD25 super(+) T-cells prevented spontaneous diabetes, even when given to rats age 42 days, whereas 20 million CD4 super(+)CD25 super(-) cells (with low Foxp3 expression) were far less effective. We thus demonstrated that CD4 super(+)CD25 super(+) cells exhibit powerful regulatory potential in rat diabetes.
ISSN:0012-1797