Predominant immature CD8alpha+ 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 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.
Xu
Lin
L
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Guangdong Province, China.
Duan
Lianning
L
Cao
Kaiyuan
K
Yuan
Guangqing
G
Peng
Yanwen
Y
Huang
Xiaorong
X
Xiang
Peng
P
Li
Shunong
S
D000818:Animals; D016026:Bone Marrow Transplantation; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D051379:Mice; D046529:Microscopy, Electron, Transmission; D012307:Risk Factors; D055502:Secondary Prevention; D015996:Survival Rate; D014184:Transplantation, Homologous
D016827:CD8 Antigens; C431698:CD8alpha antigen