T cell is the major factor mediating the pathogenesis of acquired AA, which is involved with imbalanced CD4+ and CD8+ T cells subpopulation. CD4+ T cells were commonly divided into helper T lymphocyte (Th1), Th2, Th17 and CD4+CD25+ FOXP3+ regulatory T cells (Tregs). Th1 cells and cytotoxic T lymphocytes (CTLs) are activated while Tregs are deficient, and Th2 cells are almost normal or expanded in AA [[3], [4], [5], [6] and [7]]. Aberrant immune cells directly and indirectly destruct HSCs by secreting a variety of immune molecules including tumor necrosis factor-α (TNF-α), interferon-γ Protease Inhibitor Library mw (IFN-γ) and interleukins (IL-2,

8, 12, 15, 17, 27) [1,[8], [9] and [10]]. As a result, HSCs are severely impaired to be disabled cells leading to hypoplasia and pancytopenia. AZD6244 Lots of evidence has hinted that AA might be a syndrome characterized by stem/progenitor-cell disorders including HSCs/HPCs and bone marrow mesenchymal stem cells (BM-MSCs). Previous studies

have demonstrated that HSCs/HPCs from AA patients are defective in multiple biological properties and functions [[11], [12] and [13]]. Besides the role of HSCs/HPCs in the process of hematopoisis, BM-MSCs as the key precursor cells of marrow microenvironment may also play an important role in the development of AA. MSCs differentiate into a variety of stromal cells to constitute HSC niche, which include endothelial cells, adipocytes, fibroblasts, osteoblasts and osteoclasts etc. MSCs and differentiated stromal cells support hematopoiesis and regulate almost overall immune cells function to maintain the hematopoietic and immune homeostasis [[14] and [15]]. MSCs can modulate the major immune cell functions including T, B, monocytes, dendritic cells (DCs), nature killer cells (NKs) and neutrophils [[16] and [17]]. MSCs possess remarkable immunosuppressive properties on Th1 and CTLs. MSCs inhibit the

proliferation of T cells, IFN-γ and TNF-α secretion by Th1 cells while promoting IL-10 production by Th2 cells and the expansion Oxymatrine of Tregs. However, it is controversial about the immunomodulation of MSCs on IL-4 and IL-17 production by Th2 and Th17 cells [[18] and [19]]. Recently, sporadic research showed that MSCs from AA patients had poor proliferation and deficient immune suppression of MLR, PHA-induced T cell activation and IFN-γ release [[20] and [21]]. T lymphocyte is known to be the major executor of the adaptive immune response and the arch-criminal of hematopoiesis destruction in AA. During the development of AA, Th1 and Th17 cells are expanded while Tregs are reduced [7]. However, it is still controversial about the levels and functions of Th2 cells [3,7]. It is necessary to determine whether BM-MSCs contribute to the aberrant immunomodulation process mediated by CD4+ T cells in AA.