Abnormalities of quantities and functions of natural killer cells in severe aplastic anemia

Abstract

Severe aplastic anemia (SAA) is a rare disease characterized by severe pancytopenia and bone marrow failure. Natural killer (NK) cells are large granular lymphocytes derived from hematopoietic stem cells (HSCs) or common lymphoid progenitors (CLP). They play a key role in n the innate immunity and adaptive immune. In this study, the quantitative and functional changes of natural killer (NK) cell subsets in peripheral blood of severe aplastic anemia (SAA) patients before and after immunosuppressive therapy (IST) were investigated. Results showed that the percentage of NK cells and its subsets in peripheral blood lymphocytes was decreased in SAA patients. After IST, the percentage of NK cells and their subsets increased dramatically. The median expressions of CD158a, NKG2D and NKp46 on NK cells were higher in SAA patients compared to that in normal controls, and the expressions of perforin in newly diagnosed and recovery SAA patients were higher than that in controls. Therefore, we concluded that the decrease of total NK cells, and CD56(bright), CD56(dim) NK cell subsets and the higher expressions of NKp46 and perforin on NK cells may cause the over-function of T lymphocytes and thus lead to hematopoiesis failure in SAA.

SulfatedRadix Cyathulae officinalisPolysaccharides Act as Adjuvant via Promoting the Dendritic Cell Maturation and Suppressing Treg Frequency

“…NK cells and CTLs represent two major populations of cytotoxic lymphocytes Liu et al, 2014;Shimada et al, 2014;Xu et al, 2009) and are important in defense against tumors and viruses by effector molecules, such as perforin, Gra B, Fas L, and Fas, or by indirectly interfering with the replication of the virus (Moretta et al, 2001). NK cells and CTLs can kill autologous cells infected with intracellular pathogens.…”

Proteomics analysis reveals alterations of NK cells in patients with severe aplastic anemia

“…11 Our previous studies showed that the percentage of peripheral blood NK cells and their subsets were lower in untreated SAA patients, and increased after immunosuppressive therapy, particularly the CD56 bright NK subsets. 12 Meanwhile, NKp46 receptor on NK cells from SAA patients increased, suggesting that NK cells may play a "protective" role instead of a "pathogenic" role. 13 Further studies demonstrated that the killing effect of NK cells from SAA patients increased in vitro.…”

Molecular pathogenesis of acquired aplastic anemia

“…The mechanisms of immune escape of these HSCs from NK cells remain to be fully understood but may have to do with dysfunction of the immune system that could potentially be restored by immune modulatory intervention such as with IST. In accordance with this, NK cell lymphocyte subsets are severely reduced in active AA and increase dramatically following response to IST . The NKG2D protein‐ligand system represents one of the best characterized pathways in NK cell‐mediated immunity.…”

“…In accordance with this, NK cell lymphocyte subsets are severely reduced in active AA and increase dramatically following response to IST. 58 The NKG2D protein…”