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Predominant immature CD8 α + dendritic cells prevent graft‐vs.‐host disease but do not increase the risk of leukemia recurrence
Author(s) -
Xu Lin,
Duan Lianning,
Cao Kaiyuan,
Yuan Guangqing,
Peng Yanwen,
Huang Xiaorong,
Xiang Peng,
Li Shug
Publication year - 2007
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2006.00804.x
Subject(s) - leukemia , cd8 , immunology , bone marrow , transplantation , medicine , in vivo , graft versus host disease , cancer research , immune system , biology , microbiology and biotechnology
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 CD8 α + 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 CD8 α + 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 CD8 α + on day 3. These DC were identified as morphologically and phenotypically immature CD8 α + DC. The suppressive function was observed in vitro , and then in vivo on allo‐BMT leukemia model. The prepared predominant immature CD8 α + 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 CD8 α + DC leukemia mice reached long‐term survival. Although predominant immature CD8 α + 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.