1 INTRODUCTION
Acquired aplastic anemia (AA) is characterized by pancytopenia caused by
bone marrow failure without dysplasia or fibrosis. Both clinical and
laboratory evidence support that pathogenesis of bone marrow failure is
due to injury to hematopoietic stem cells (HSCs) by abnormal
immunity1,2. Overall, research on depletion of HSCs in
AA has focused on exploring the mechanism by which abnormal immunity
attacks HSCs. However, no specific antibodies or immune cells targeting
HSCs have been found to date. Therefore, the ”immune-mediated
pathogenesis” of AA has not yet clarified how immune disorders
specifically damage HSCs rather than other cells in bone marrow.
With in-depth study of bone marrow microenvironment, immune privileged
(IP) sites of bone marrow specific to HSCs are
discovered3. IP sites are mainly comprised of
CD4+CD25+FoxP3+regulatory T cells (Tregs) which surround HSCs near the endosteal
surface, providing an immune tolerance microenvironment for HSCs to
protect HSCs from infection, radiation and other stress damage. This
urged us to shift the research on depletion mechanism of HSCs in AA from
immune “attack” to “protection loss” of IP. In fact, IP sites also
exist in other tissues, and their abnormal pathogenicity has been a
concern in various diseases4. For example, IP sites in
hair follicle provide protection for epithelial hair follicle stem
cells, and functional impairment leads to destruction of epithelial hair
follicle stem cells, which is the main pathological mechanism of
persistent alopecia in alopecia areata5. The local
immune tolerance status of IP sites can be determined by detecting
FoxP3+/CD4+ cells with an
immunohistochemical method6. But the correlation
between the collapse of self-tolerance of bone marrow IP sites and AA
has not been reported. This study aimed to clinically verify that HSCs
failure in AA is closely related to IP abnormalities through the
detection of bone marrow IP sites in AA, MDS, and countrol group,
providing clinical supportive evidence of worth further study for the IP
pathogenesis in AA.