A limited course of soluble CD83 delays acute cellular rejection of MHC-mismatched mouse skin allografts.
CD83 is a surface marker expressed on matured dendritic cells (DCs). It plays a pivotal role in the mediation of DC/T cell interaction and induction of T-cell activation. Previous studies have suggested that a soluble form of CD83 could suppress DC maturation and inhibit T-cell activation and, as a result, it can prevent paralysis associated with experimental autoimmune encephalomyelitis. Here, we explored its potential effect on allograft rejection in a fully major histocompatibility complex-mismatched murine skin transplantation model. A form of mouse soluble CD83 (CD83-Ig) fused the extracellular domain of murine CD83 with human IgG1alpha Fc tail was purified from transfected COS-7 cell. It was found that the treatment of recipient mice with CD83-Ig significantly delayed allograft rejection. Especially, when T cells originated from recipients treated with CD83-Ig re-stimulated with donor-specific splenocytes, they showed a significant reduced responding capability as compared with that of originated from control recipients. In line with these results, a reduction for serum IFN-gamma and IL-2 and a decreased mRNA expression of IFN-gamma and IL-2 in allograft infiltrated immune cells were also observed. Our results suggest that CD83-Ig could be useful for the treatment of allograft rejection in combination with other therapeutic strategies.
Xu
Jun-Fa
JF
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Huang
Bao-Jun
BJ
Yin
Hui
H
Xiong
Ping
P
Feng
Wei
W
Xu
Yong
Y
Fang
Min
M
Zheng
Fang
F
Wang
Cong-Yi
CY
Gong
Fei-Li
FL
D000818:Animals; D015703:Antigens, CD / Q000627:therapeutic use*; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007136:Immunoglobulins / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D000097802:CD83 Antigen
D015703:Antigens, CD; D016207:Cytokines; D007074:Immunoglobulin G; D007136:Immunoglobulins; D007371:Interferon-gamma; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen