Submitted December 20, 2007
Accepted January 24, 2008
Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+CD25+ FOXP3+ regulatory T cells
Sarah T.A. Roord, Wilco de Jager, Louis Boon, Nico Wulffraat, Anton Martens, Berent Prakken*, and Femke van Wijk
Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, Netherlands
Bioceros B.V., Utrecht, Netherlands
Department of Hematology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, Netherlands
* Corresponding author; email: b.prakken{at}umcutrecht.nl.
Despite the earlier use of potent immunosuppressive or cytostatic drugs and the recent emergence of biologicals as treatment for human Autoimmune Diseases (AID), some patients still remain unresponsive to treatment. To those severely ill patients autologous Bone Marrow Transplantation (aBMT) is applied as a last resource, leading to disease remission in a majority of patients. The underlying mechanism of action of aBMT is still largely unknown.
Here, we showed that regulatory T cells (Tregs) play a role in the natural disease course of Proteoglycan Induced Arthritis (PGIA) and in disease remission by aBMT. ABMT led to an initial phase of rapid disease improvement corresponding with a relative increase in CD4+CD25+ T cells. At this time the CD4+CD25+ cells did not show an increase in Foxp3 expression yet and showed less potent suppression. After this initial improvement disease relapsed but stabilised at a level below the severity before aBMT. This second phase was actively regulated by potently suppressive CD4+CD25+Foxp3+ Tregs.
This work provided further insight into the role of Tregs in restoration of the immune balance by aBMT and can open the way to explore therapeutical interventions to further improve treatment of AID and disease relapses.
