Antithymocyte globulin treatment at the time of transplantation impairs donor hematopoietic stem cell engraftment.
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.
The First Hospital of Jilin University, Changchun, China.|Institute of Immunology, Jilin University, Changchun, China.
Feng
F
Jin
The First Hospital of Jilin University, Changchun, China.
Jin
J
He
The First Hospital of Jilin University, Changchun, China.|Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Chunhui
C
Jin
The First Hospital of Jilin University, Changchun, China.|Institute of Immunology, Jilin University, Changchun, China.
Wei
W
Fan
The First Hospital of Jilin University, Changchun, China.
Yanhong
Y
Shan
The First Hospital of Jilin University, Changchun, China.
Zhefeng
Z
Zhang
The First Hospital of Jilin University, Changchun, China.|Institute of Immunology, Jilin University, Changchun, China.
Liguang
L
Sun
The First Hospital of Jilin University, Changchun, China.|Institute of Immunology, Jilin University, Changchun, China.
Zheng
Z
Hu
The First Hospital of Jilin University, Changchun, China.|Institute of Immunology, Jilin University, Changchun, China.|Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Yong-Guang
YG
Yang
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents