Abstract
A series of immune abnormalities presenting in aplastic anemia (AA)
support the immune pathogenesis of AA. However, how abnormal immunity
specifically damages hematopoietic stem cells (HSCs) remains ambiguous.
The discovery of bone marrow immune privilege (IP) sites which are
composed of
CD4+CD25+FoxP3+regulatory T cells (Tregs) exclusively to protect HSCs prompted us
boldly assumed that it is a loss of IP protection leading to HSCs
exhausted in AA. A experiment study to clinically confirm the
correlation between HSCs depletion and IP abnormalities in patients with
AA was conducted. The distribution of Tregs in bone marrow from children
with AA, myelodysplastic syndrome (MDS) and control group was detected
by immunohistochemistry. Th1, Th2, Th17 and HSCs as well as cytokines in
bone marrow of these children were examined by flow cytometry. Tregs
near endostea surface of bone marrow of children with AA was
significantly lower than that in control and MDS. Th1 was more
predominant in AA than in the control children. TNF-α, IFN-γ and IL-17
levels were also increased in AA. Compared to the control group, HSCs in
bone marrow of AA, including Long-term HSCs (LT-HSCs) and Short-term
HSCs (ST-HSCs), were at lower level. The results indicate that HSCs
depletion is closely related to bone marrow IP abnormalities in AA, and
the role of IP abnormalities in the pathogenesis of aplastic anemia
deserves further research.