Anti-gamma chain and anti-IL-2Rbeta mAbs in combination with donor splenocyte transfusion induce H-Y skin graft acceptance in murine model.
BACKGROUND
The common cytokine receptor gamma chain signals regulate proliferation, differentiation, and apoptosis of peripheral T cells.


OBJECTIVE
To investigate whether simultaneous blockade of IL-2Rbeta and gamma chain signaling in combination with donor splenocyte transfusion (DST) induces transplant tolerance.


METHODS
C57BL/6 (H-2b) mice were randomly divided into 5 groups. In group 1, female mice received only H-Y skin grafts. In group 2, female mice received transfused splenocytes (5 x 10(6) cells) from syngeneic male mice on day 7 before H-Y skin grafting. In group 3, on days 2 and 4 after DST, female mice received intraperitoneal injections of a mixture of anti-IL-2Rbeta monoclonal antibody (mAb) and anti-gamma chain mAbs (4G3, 3E12, and TUGm2; 0.5 mg). After DST, group 4 received an intraperitoneal injection of the mixture of anti-gamma chain mAbs, and group 5 received intraperitoneal injection of anti-IL-2Rbeta mAb (TM-beta1). On day 7, H-Y skin grafting was performed.


RESULTS
Group 3 recipients accepted H-Y skin grafts for more than 100 days compared with group 1 (mean survival time [MST], 33.42 days), group 2 (MST, 14.71 days), group 4 (MST, 58.71 days), and group 5 (MST, 17.29 days). Statistical differences (P < .05) were observed between any 2 groups except groups 2 and 5.


CONCLUSIONS
Blockade of gamma chain signaling rather than IL-2Rbeta signaling combined with DST prolongs H-Y skin graft survival. Simultaneous blockade of IL-2Rbeta and gamma chain signaling may strengthen this effect.
Chang
S
S
Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chen
B-C
BC
Du
D-F
DF
Zhou
J
J
Zhang
X
X
Chen
Z-H
ZH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology / Q000627:therapeutic use*; D000939:Epitopes / Q000276:immunology; D006085:Graft Survival / Q000502:physiology*; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology* / Q000502:physiology; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D016038:Skin Transplantation / Q000502:physiology*; D013154:Spleen / Q000166:cytology* / Q000637:transplantation; D013623:Tail; D023001:Transplantation Tolerance / Q000187:drug effects / Q000502:physiology*; D014185:Transplantation, Isogeneic / Q000502:physiology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D053631:Interleukin Receptor Common gamma Subunit; D053646:Interleukin-2 Receptor beta Subunit