Blockade of gammac signals in combination with donor-specific transfusion induces cardiac allograft acceptance in murine models.
The gammac cytokines play an important role in proliferation and survival of T cells. Blocking the gammac signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the gammac in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-gammac monoclonal antibodies (mAbs) injection, and those in control group were not given anti-gammac mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of gammac signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.
Chang
Sheng
S
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. changsheng2000@126.com
Wang
Li
L
Lin
Xingguang
X
Xiang
Fuli
F
Chen
Bicheng
B
Chen
Zhonghua
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D017690:Cell Transplantation / Q000379:methods; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D053631:Interleukin Receptor Common gamma Subunit / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D061166:Peripheral Tolerance; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects
D000911:Antibodies, Monoclonal; D053631:Interleukin Receptor Common gamma Subunit