title: Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice.
abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H×Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China.
authors.forename: Suigui
authors.initials: S
authors.lastname: Wan
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Yu
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. Electronic address: cqx65@yahoo.com.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Xia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects* / Q000637:transplantation*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D016753:Interleukin-10
keywords: Dendritic cells; Graft-versus-host disease; Haploidentical; Hematopoietic stem cell transplantation; Immune tolerance; Regulatory T cells