CD8α+ plasmacytoid precursor DCs induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo
| Autor: | Hong Xu, Yiming Huang, Larry D. Bozulic, Suzanne T. Ildstad, Thomas Miller, Lala-Rukh Hussain |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD8 Antigens Immunology Population Bone Marrow Cells T-Cell Antigen Receptor Specificity chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Biochemistry Immunophenotyping Mice Animals Transplantation Homologous IL-2 receptor education Transplantation Chimera Transplantation education.field_of_study Graft Survival Hematopoietic Stem Cell Transplantation FOXP3 hemic and immune systems Dendritic Cells Cell Biology Hematology Dendritic cell Haematopoiesis Cancer research Stem cell CD8 |
| Zdroj: | Blood. 117:2494-2505 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2010-06-291187 |
| Popis: | CD8-positive/T-cell receptor–negative (CD8+/TCR−) graft facilitating cells (FCs) are a novel cell population in bone marrow that potently enhance engraftment of hemopoietic stem cells (HSCs). Previously, we showed that the CD11c+/B220+/CD11b− plasmacytoid-precursor dendritic cell (p-preDC) FC subpopulation plays a critical but nonredundant role in facilitation. In the present study, we investigated the mechanism of FC function. We report that FCs induce antigen-specific CD4+/CD25+/FoxP3+ regulatory T cells (Tregs) in vivo. The majority of chimeric Tregs were recipient derived. Chimeric Tregs harvested at ≥ 4 weeks after transplantation significantly enhanced engraftment of donor- and recipient-derived HSCs, but not third-party HSCs, in conditioned secondary recipients, demonstrating antigen specificity. Although Tregs were present 2 and 3 weeks after transplantation, they did not enhance engraftment. In contrast, week 5 and greater Tregs potently enhanced engraftment. The function of chimeric Tregs was directly correlated with the development of FoxP3 expression. Chimeric Tregs also induced significantly stronger suppression of T-cell proliferation to donor antigen in vitro. Removal of p-preDC FCs resulted in impaired engraftment of allogeneic HSCs and failure to produce chimeric Tregs, suggesting that the CD8α+ p-preDC subpopulation is critical in the mechanism of facilitation. These data suggest that FCs induce the production of antigen-specific Tregs in vivo, which potently enhance engraftment of allogeneic HSCs. FCs hold clinical potential because of their ability to remain tolerogenic in vivo. |
| Databáze: | OpenAIRE |
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