Abstract
Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8+ cytotoxic T cells, CD4+ T cells including T helper type 1 (Th1), Th2, regulatory T cells and Th17 cells, natural killer (NK) cells and NK T cells, along with the abnormal production of cytokines including interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-β, IFN-γ and TNF-α genes, as well as certain human leucocyte antigen (HLA) alleles, may account for the propensity to immune-mediated killing of HSPCs and/or ineffective haematopoiesis. Although the inciting autoantigens remain elusive, autoantibodies are often detected in the serum. In addition, recent studies provide genetic and molecular evidence that intrinsic and/or secondary deficits in HSPCs and bone marrow mesenchymal stem cells may underlie the development of bone marrow failure.
Original language | English (US) |
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Pages (from-to) | 361-370 |
Number of pages | 10 |
Journal | Clinical and Experimental Immunology |
Volume | 180 |
Issue number | 3 |
DOIs | |
State | Published - Jun 1 2015 |
Keywords
- Aplastic anemia
- Bone marrow mesenchymal stem cell
- Hematopoietic stem/progenitor cell, immune dysregulation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology