Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+CD25+FoxP3+ regulatory T cells

Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, USA.
Blood (Impact Factor: 10.45). 06/2008; 111(10):5233-41. DOI: 10.1182/blood-2007-12-128488
Source: PubMed


Despite the earlier use of potent immunosuppressive or cytostatic drugs and the recent emergence of biologicals as treatment for human autoimmune diseases (AIDs), 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 yet show an increase in Foxp3 expression and showed less potent suppression. After this initial improvement, disease relapsed but stabilized 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 therapeutic interventions to further improve treatment of AID and disease relapses.

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    • "To identify the Treg cells in murine splenocytes and TACs, splenocytes and TACs were first stained with PE/Cy5-conjugated anti-mouse CD4 (eBioscience) and PE-conjugated anti-mouse CD25 (eBioscience) for cell surface markers. Fluorescein isothiocyanate-conjugated anti-mouse FoxP3 (eBioscience) for intracellular staining were performed as described previously [24]. Staining was characterized by flow cytometric analysis as described earlier. "
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