Phytohemagglutinin-activated human T cells induce lethal graft-versus-host disease in cyclophosphamide and anti-CD122 conditioned NOD/SCID mice.

Abstract

Graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation. Much of our knowledge regarding GVHD comes from experiments on the mouse hematopoietic system due to ethical and technical constraints. Thus, in vivo GVHD models of the human immune system are required. In this study, we report an effective and reliable protocol for xenogeneic GVHD (xeno-GVHD) model induction using NOD/SCID mice, in which mice underwent a conditioning regimen consisting of intraperitoneal injection of cyclophosphamide and anti-CD122, followed by transfusion of phytohemagglutinin-activated human peripheral blood mononuclear cells containing 1 × 10⁷ T cells, which has not been reported previously. The present model can be utilized to study human immune cell function in vivo and elucidate the mechanisms underlying the pathogenesis of human GVHD. In addition, this model system can help researchers to rapidly determine whether proposed therapeutic strategies for GVHD are efficient in vivo and will elucidate the underlying mechanisms of drugs and cells to be investigated. Furthermore, such a protocol will undoubtedly be very helpful to laboratories that have no available sources of irradiation.

• Authors: Yongxian Hu, Yanjun Gu, Qu Cui, Huarui Fu, Lixia Sheng, Kangni Wu, Lizhen Liu, Shan Fu, Xiaohong Yu, He Huang
• Journal: Annals of hematology (Ann Hematol) Vol. 91 Issue 11 Pg. 1803-12 (Nov 2012) ISSN: 1432-0584 [Electronic] Germany
• PMID: 22699803 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Il2rb protein, mouse
• Immunosuppressive Agents
• Interleukin-2 Receptor beta Subunit
• Mitogens
• Phytohemagglutinins
• Cyclophosphamide

Topics

• Animals
• Autoantibodies (therapeutic use)
• Crosses, Genetic
• Cyclophosphamide (therapeutic use)
• Disease Models, Animal
• Graft Survival
• Graft vs Host Disease (etiology, immunology, pathology)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Interleukin-2 Receptor beta Subunit (antagonists & inhibitors)
• Lymphocyte Activation
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Mitogens
• Phytohemagglutinins
• Specific Pathogen-Free Organisms
• T-Lymphocytes (immunology, transplantation)
• Transplantation Conditioning (methods)
• Transplantation, Heterologous (immunology, methods)