Predominant immature CD8α+ dendritic cells prevent graft-vs.-host disease but do not increase the risk of leukemia recurrence
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 CD8α+ 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 CD8α+ 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 CD8α+ on day 3. These DC were identified as morphologically and phenotypically immature CD8α+ DC. The suppressive function was observed in vitro, and then in vivo on allo-BMT leukemia model. The prepared predominant immature CD8α+ 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 CD8α+ DC leukemia mice reached long-term survival. Although predominant immature CD8α+ 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.
Document Type: Research Article
Affiliations: 1: The Department of Laboratory Medicine, Zhongshan Medical School, Sun Yat-sen University, Guangdong Province, China 2: Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Guangdong Province, China
Publication date: March 1, 2007