| First Author | Erie AJ | Year | 2011 |
| Journal | Exp Hematol | Volume | 39 |
| Issue | 8 | Pages | 837-49 |
| PubMed ID | 21635935 | Mgi Jnum | J:186746 |
| Mgi Id | MGI:5433000 | Doi | 10.1016/j.exphem.2011.05.005 |
| Citation | Erie AJ, et al. (2011) MHC class II upregulation and colocalization with Fas in experimental models of immune-mediated bone marrow failure. Exp Hematol 39(8):837-49 |
| abstractText | OBJECTIVE: To test the hypothesis that gamma-interferon (IFN-gamma) promotes major histocompatibility complex (MHC) class II expression on bone marrow (BM) cell targets that facilitate T-cell-mediated BM destruction in immune-mediated BM failure. MATERIALS AND METHODS: Allogeneic lymph node (LN) cells were infused into MHC- or minor histocompatibility antigen-mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas colocalization was detected by ImageStream Imaging Flow Cytometry and other cell-to-cell associations were visualized by confocal microscopy. T-cell-mediated BM cell apoptosis and effects of IFN-gamma on MHC class II-Fas colocalization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry. RESULTS: BM failure animals had significantly upregulated MHC class II expression on CD4(-)CD8(-)CD11b(-)CD45R(-) residual BM cells and significantly increased MHC class II-Fas colocalization on BM CD150(+) and CD34(+) hematopoietic cells. MHC class II(+)Fas(+) BM cells were closely associated with CD4(+) T cells in the BM of affected animals, and they were significantly more responsive to T-cell-mediated cell apoptosis relative to MHC class II(-)Fas(-) BM cells. Infusion of IFN-gamma-deficient LN cells into minor histocompatibility antigen-mismatched recipients resulted in no MHC class II-Fas upregulation and no clinically overt BM failure. Treatment with recombinant IFN-gamma significantly increased both MHC class II-Fas coexpression and colocalization on normal BM cells. CONCLUSIONS: Elevation of the inflammatory cytokine IFN-gamma-stimulated MHC class II expression and MHC class II-Fas colocalization, which may facilitate T-cell-mediated cell destruction. |
