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Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+CD25+Foxp3+ regulatory T cells.

Abstract
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.
AuthorsSarah T A Roord, Wilco de Jager, Louis Boon, Nico Wulffraat, Anton Martens, Berent Prakken, Femke van Wijk
JournalBlood (Blood) Vol. 111 Issue 10 Pg. 5233-41 (May 15 2008) ISSN: 1528-0020 [Electronic] United States
PMID18256318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Proteoglycans
Topics
  • Animals
  • Arthritis (therapy)
  • Autoimmune Diseases
  • Bone Marrow Transplantation (methods)
  • CD4 Lymphocyte Count
  • Female
  • Hemostasis
  • Humans
  • Immune System (physiology)
  • Mice
  • Mice, Inbred BALB C
  • Proteoglycans
  • Remission Induction
  • T-Lymphocytes, Regulatory (physiology)
  • Transplantation, Autologous
  • Treatment Outcome

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