Acquired aplastic anemia (AA) is considered as an immune-mediated bone marrow failure syndrome, characterized by hypoplasia and pancytopenia with fatty bone marrow. Abnormal immunity is the major factor mediating the pathogenesis of acquired AA. Activated DCs might promote the polarization to Th1 cells, and activate CD8(+) T cells. A variety of immune molecules including IFN-gamma, TNF-alpha, MIP-1alpha and IL-2, 8, 12, 15, 17, 23, produced by them and stromal cells, compose a cytokine network to destruct stem/progenitor cells as well as hematopoietic stem/progenitor cells, mesenchymal stem cells (MSCs) and angioblasts/endothelial progenitor cells. Inversely, deficient MSCs, CD4(+)CD25(+) T cells, NK cells, NKT cells and early hematopoietic growth factors diminish the capacity of immune regulation and the support of hematopoiesis. As a result, stem/progenitor cells are significantly impaired to be disabled cells with markedly deficient proliferation, differentiation, induced apoptosis and dysfunctional response to growth factor stimuli, together with rare normal ones. Although some patients can be ameliorated by stem-cell transplantation or immunosuppressive therapy, more effective and convenient therapies such as patient-specific pluripotent iPS cells based on definite pathogenesis are expected.
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