Phytohemagglutinin-activated human T cells induce lethal graft-versus-host disease in cyclophosphamide and anti-CD122 conditioned NOD/SCID mice.
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.
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Yongxian
Y
Hu
Yanjun
Y
Gu
Qu
Q
Cui
Huarui
H
Fu
Lixia
L
Sheng
Kangni
K
Wu
Lizhen
L
Liu
Shan
S
Fu
Xiaohong
X
Yu
He
H
Huang
D000818:Animals; D001323:Autoantibodies / Q000627:therapeutic use; D003433:Crosses, Genetic; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053646:Interleukin-2 Receptor beta Subunit / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008934:Mitogens; D010835:Phytohemagglutinins; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D019172:Transplantation Conditioning / Q000379:methods*; D014183:Transplantation, Heterologous / Q000276:immunology / Q000379:methods
D001323:Autoantibodies; C508022:Il2rb protein, mouse; D007166:Immunosuppressive Agents; D053646:Interleukin-2 Receptor beta Subunit; D008934:Mitogens; D010835:Phytohemagglutinins; D003520:Cyclophosphamide