Kinetics, function and bone marrow trafficking of CD4 super(+) CD25 super(+) FOXP3 super(+) regulatory T cells in myelodysplastic syndromes (MDS)

• Published in: Leukemia Vol. 23; no. 3; pp. 510 - 518
• Main Authors: Kotsianidis, I, Bouchliou, I, Nakou, E, Spanoudakis, E, Margaritis, D, Christophoridou, A V, Anastasiades, A, Tsigalou, C, Bourikas, G, Karadimitris, A, Tsatalas, C
• Format: Journal Article
• Language: English
• Published: 01.03.2009
• ISSN: 0887-6924
• DOI: 10.1038/leu.2008.333

CD4 super(+) CD25 super(+) FOXP3 super(+) T regulatory cells (T sub(regs)) prevent autoimmunlty by restricting overexuberant immune responses, but the same subpopulatlon can incur detrimental effects on antitumor responses. In both cases, the suppressor potential of T sub(regs) appears to be strongly influenced by their compartmentalizatlon. In myelodysplastic syndromes (MDS), immune deregulation and autoimmunity In the early stages might lead to ineffective hematopolesis and bone marrow (BM) failure, whereas late-stage disease is characterized by the immune escape of the malignant clone. We show that these two stages of MDS are associated with differential T sub(reg) activity. Specifically, we found that In early stage MDS, compared with normal hematopoiesis and late stage MDS, T sub(regs) are dysfunctional and their BM homing through the CXCL12/CXCR4 axis is seriously impaired as a result of CXCR4 downregulatlon. Conversely, in late stage MDS, T sub(regs) are systemically and locally expanded and retain their function and migratory capacity. Moreover, T sub(reg)levels follow the disease course and are significantly reduced in treatment responding patients. Our findings indicate T sub(reg)Involvement In the pathophysiology of MDS; defective suppressor function and BM trafficking of T sub(regs) may be Important In the autoimmune process of early MDS, but increased T sub(reg)activity could favor leukemlc clone progression in late stage disease.