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Antithymocyte globulin treatment at the time of transplantation impairs donor hematopoietic stem cell engraftment

Cellular & Molecular Immunology volume 14, pages 443–450 (2017)Cite this article

Abstract

Antithymocyte globulin (ATG) is often included in the conditioning regimen to prevent graft vs. host disease in allogeneic hematopoietic stem cell (HSC) transplantation. However, because ATG contains antibodies targeting a wide range of antigens on human cells, its potential off-target effects remain a concern. Here, we explored this question in humanized mice that permit the analysis of human cell depletion in tissues. We showed that ATG binds to almost all lineages of human hematopoietic cells including HSCs, and accordingly it is capable of depleting almost all human hematopoietic cells. Interestingly, the efficacy of ATG was highly variable depending on the tissue of residence, with human cells in bone marrow significantly less susceptible than those in the blood and spleen. Recovery of multilineage human lymphohematopoietic reconstitution in humanized mice that received ATG 3 weeks after HSC transplantation indicates that ATG had a minimal effect on human HSCs that have settled in bone marrow niches. However, efficient human HSC depletion and engraftment failure were seen in mice receiving ATG at the time of transplantation. Our data indicate that the efficacy of ATG is tissue-dependent, and suggest a potential risk of impairing donor hematopoietic engraftment when ATG is used in preparative conditioning regimens.

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Acknowledgements

The authors thank Ms. Meifang Wang and Mr. Zhifu Gan for their excellent animal care. This work was supported by grants from Chinese MOST (973 Program 2015CB964400 and 2013CB966900; 863 Program 2014AA021601), NSFC (81200397, 81273334), National Science and Technology Major Project of China (2013ZX10002008), Chinese Ministry of Education (IRT1133), and NIH (P01AI045897). Supplementary information of this article can be found on the Cellular & Molecular Immunology’s website (http://www.nature.com/cmi).

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Author notes

  1. Z Hu and Y-G Yang, The First Hospital of Jilin University, Changchun China. E-mail: zhenghu0108@outlook.com; yy2324@columbia.edu

Authors and Affiliations

  1. The First Hospital of Jilin University, Changchun, China

    Feng Jin, Jin He, Chunhui Jin, Wei Fan, Yanhong Shan, Zhefeng Zhang, Liguang Sun, Zheng Hu & Yong-Guang Yang

  2. Institute of Immunology, Jilin University, Changchun, China

    Feng Jin, Wei Fan, Liguang Sun, Zheng Hu & Yong-Guang Yang

  3. Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Chunhui Jin & Yong-Guang Yang

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  1. Feng Jin
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Supplementary information of this article can be found on the Cellular & Molecular Immunology’s website (http://www.nature.com/cmi).

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Jin, F., He, J., Jin, C. et al. Antithymocyte globulin treatment at the time of transplantation impairs donor hematopoietic stem cell engraftment. Cell Mol Immunol 14, 443–450 (2017). https://doi.org/10.1038/cmi.2015.92

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