Predominant immature CD8?+dendritic cells prevent graft-vs.-host disease but do not increase the risk of leukemia recurrence
| Autor: | Kaiyuan Cao, Xiao-rong Huang, Peng Xiang, Shunong Li, Lin Xu, Yanwen Peng, Lianning Duan, Guang-qing Yuan |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
CD8 Antigens
Lymphocyte Graft vs Host Disease chemical and pharmacologic phenomena Stem cell factor Mice Microscopy Electron Transmission Risk Factors Secondary Prevention Animals Transplantation Homologous Medicine Bone Marrow Transplantation Leukemia business.industry Cell Differentiation hemic and immune systems Dendritic Cells Hematology General Medicine Dendritic cell medicine.disease Colony-stimulating factor Survival Rate Transplantation surgical procedures operative medicine.anatomical_structure Immunology Bone marrow Stem cell business |
| Zdroj: | European Journal of Haematology. 78:235-245 |
| ISSN: | 1600-0609 0902-4441 |
| DOI: | 10.1111/j.1600-0609.2006.00804.x |
| Popis: | Graft-vs.-host disease (GVHD) remains the major limitation of allogeneic bone marrow transplantation (BMT) and stem cell transplantation, and leukemia recurrence is another important complication in leukemia treatment. Immature CD8alpha+ dendritic cells (DC) have good potential in GVHD treatment and immunological tolerance studies. To find a new way to prevent GVHD, not increasing the risk of leukemia recurrence, in this study, predominant CD8alpha+ immature DC were induced from murine bone marrow (BM) cells by 5 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF) plus 20-ng/mL interleukin (IL)-4, 100-ng/mL stem cell factor (SCF) and 25-ng/mL Flt3L, and 97.09 of prepared DC were CD8alpha+ on day 3. These DC were identified as morphologically and phenotypically immature CD8alpha+ DC. The suppressive function was observed in vitro, and then in vivo on allo-BMT leukemia model. The prepared predominant immature CD8alpha+ DC were weak syngeneic lymphocyte stimulators and could suppress mixed leukocyte reaction in vitro. In vivo, they prevented the pathological changes of GVHD and prolonged the surviving time of allo-BMT leukemia mice. The effect showed a dose-effect relationship. 86.7% of allo-BMT plus 1 million predominant CD8alpha+ DC leukemia mice reached long-term survival. Although predominant immature CD8alpha+ DC had the function of GVHD suppression, they did not increase leukemia recurrence. The method and findings may have important potency for GVHD treatment in clinical application. |
| Databáze: | OpenAIRE |
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