Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia; Yu, Xue-Zhong; Xia, Chang-Qing

doi:10.1016/J.BBRC.2014.03.055

Title: Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

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Abstract

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - 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 (C3Hmore »« less

Authors:

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia ^[1]; Yu, Xue-Zhong ^[2]; Xia, Chang-Qing ^[1]

Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States)

Publication Date:: Fri Apr 18 00:00:00 EDT 2014

OSTI Identifier:: 22416385

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 446; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; ANTIGENS; BONE MARROW; BONE MARROW CELLS; CHILDREN; DEATH; DISEASES; GRAFTS; IMMUNITY; IMMUNOTHERAPY; INFUSION; IRRADIATION; LEUKOCYTES; MICE; PATIENTS; STEM CELLS; STRAINS; TOLERANCE; ULTRAVIOLET RADIATION

Citation Formats


                    Guo, Yixian, Zhang, Lanfang, Wan, Suigui, Sun, Xuejing, Wu, Yongxia, Yu, Xue-Zhong, and Xia, Chang-Qing. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice.  United States: N. p., 2014. 
        Web.  doi:10.1016/J.BBRC.2014.03.055.

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                    Guo, Yixian, Zhang, Lanfang, Wan, Suigui, Sun, Xuejing, Wu, Yongxia, Yu, Xue-Zhong, & Xia, Chang-Qing. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice.  United States.  https://doi.org/10.1016/J.BBRC.2014.03.055

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                    Guo, Yixian, Zhang, Lanfang, Wan, Suigui, Sun, Xuejing, Wu, Yongxia, Yu, Xue-Zhong, and Xia, Chang-Qing. 2014.  
        "Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice".  United States.  https://doi.org/10.1016/J.BBRC.2014.03.055.

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@article{osti_22416385,

  title        = {Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice},

  author       = {Guo, Yixian and Zhang, Lanfang and Wan, Suigui and Sun, Xuejing and Wu, Yongxia and Yu, Xue-Zhong and Xia, Chang-Qing},

  abstractNote = {Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - 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.},

  doi          = {10.1016/J.BBRC.2014.03.055},

  url          = {https://www.osti.gov/biblio/22416385},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 4,

  volume       = 446,

  place        = {United States},

  year         = {Fri Apr 18 00:00:00 EDT 2014},

  month        = {Fri Apr 18 00:00:00 EDT 2014}

}

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