International Immunology Advance Access originally published online on March 4, 2005
International Immunology 2005 17(4):429-437; doi:10.1093/intimm/dxh223
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Expression of membrane-bound IL-15 by bone marrow fibroblast-like stromal cells in aplastic anemia
1 Medical Biotechnology Institute, Clinical Immunology Key Laboratory of Jiangsu Province, Soochow University, Suzhou 215007, China
2 Research Department, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China
3 Department of Hematology, No. 2 Affiliated Hospital of Soochow University, Suzhou 215004, China
Correspondence to: Z. Xueguang; E-mail: smbxuegz{at}public1.sz.js.cn
In order to explore the relationship between IL-15 and aplastic anemia (AA), bone marrow (BM) fibroblast-like stromal cells (BMFSCs) were obtained from BM samples of 23 AA patients by density centrifugation and primary culturing in vitro. Indirect immunofluorescence labeling as well as flow cytometry and confocal laser scanning microscopy analysis were used to determine the expression of membrane-bound IL-15 (mIL-15) on the surface of BMFSCs derived from AA patients (AA-BMFSCs). The effects of IFN-
and cyclosporin A (CsA) on the expression of mIL-15 were also investigated. [3H]thymidine incorporation test as well as specific antibody inhibition and Transwell separation experiment was adopted to functionally evaluate the expression of mIL-15 on the surface of AA-BMFSCs. mIL-15 was found to be over-expressed on the surface of AA-BMFSCs. IFN- further significantly up-regulated its expression, which, however, was inhibited by CsA. Interestingly, a tight correlation was found between the expression of mIL-15 and IL-15R
on the surface of AA-BMFSCs. AA-BMFSCs had the capability to stimulate the proliferation of T lymphocytes, which was partly or completely inhibited by using neutralizing anti-IL-15R antibody, neutralizing anti-IL-15 antibody, blocking anti-IL-2/15Rc mAb or Transwell chambers with a 0.3-µm pore size membrane to block the direct cell-to-cell contact between AA-BMFSCs and T cells. Apparently, BMFSCs as the most important component of BM hematopoietic microenvironment usually over-express mIL-15 in AA patients. Therefore, AA-BMFSCs may indirectly participate in the T cell-mediated destruction of hematopoietic progenitors in AA by recruiting T cells to BM and stimulating them in situ.
Keywords: aplastic anemia, bone marrow, bone marrow fibroblast-like stromal cells, bone marrow stromal cells, IL-15
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