PMID- 24661874 OWN - NLM STAT- MEDLINE DCOM- 20140624 LR - 20140424 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 446 IP - 4 DP - 2014 Apr 18 TI - Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice. PG - 1035-41 LID - S0006-291X(14)00498-7 [pii] LID - 10.1016/j.bbrc.2014.03.055 [doi] AB - 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 (C3HxBalb/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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Guo, Yixian AU - Guo Y AD - Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. FAU - Zhang, Lanfang AU - Zhang L AD - Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. FAU - Wan, Suigui AU - Wan S AD - Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. FAU - Sun, Xuejing AU - Sun X AD - Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. FAU - Wu, Yongxia AU - Wu Y AD - Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. FAU - Yu, Xue-Zhong AU - Yu XZ AD - Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA. FAU - Xia, Chang-Qing AU - Xia CQ AD - Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, People's Republic of China. Electronic address: cqx65@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140321 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Cells, Cultured MH - Dendritic Cells/immunology/*radiation effects/*transplantation MH - Graft vs Host Disease/immunology/*prevention & control MH - Hematopoietic Stem Cell Transplantation/*methods MH - Humans MH - Immune Tolerance MH - Interleukin-10/immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C3H MH - T-Lymphocytes, Regulatory/immunology MH - Ultraviolet Rays OTO - NOTNLM OT - Dendritic cells OT - Graft-versus-host disease OT - Haploidentical OT - Hematopoietic stem cell transplantation OT - Immune tolerance OT - Regulatory T cells EDAT- 2014/03/26 06:00 MHDA- 2014/06/25 06:00 CRDT- 2014/03/26 06:00 PHST- 2014/03/10 00:00 [received] PHST- 2014/03/14 00:00 [accepted] PHST- 2014/03/26 06:00 [entrez] PHST- 2014/03/26 06:00 [pubmed] PHST- 2014/06/25 06:00 [medline] AID - S0006-291X(14)00498-7 [pii] AID - 10.1016/j.bbrc.2014.03.055 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Apr 18;446(4):1035-41. doi: 10.1016/j.bbrc.2014.03.055. Epub 2014 Mar 21.