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

作　　者：Feng Jin Jin He Chunhui Jin Wei Fan Yanhong Shan Zhefeng Zhang Liguang Sun Zheng Hu Yong-Guang Yang 

机构地区：[1]The First Hospital of Jilin University, Changchun, China [2]Institute of Immunology, Jilin University, Changchun, China [3]Columbla uenter for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA

出　　处：《Cellular & Molecular Immunology》2017年第5期443-450,共8页中国免疫学杂志（英文版）

摘　　要：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.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.

关 键 词：ATG TRANSPLANTATION hematopoietic stem cell humanized mice 

分 类 号：Q25[生物学—细胞生物学] Q255