title: Combination of donor splenocyte transfusion with blockade of γc signal synergizes to inhibit alloreactive T-cell proliferation and induces apoptosis.
abstract: BACKGROUND
  The common γ chain (γc) plays a critical role in regulating proliferation, differentiation, and apoptosis of peripheral T-cells. It was previously confirmed that blocking the γc signal can successfully induce transplant tolerance in a murine model. Here we investigated the potential mechanism.
  
  
  METHODS
  Splenocytes from C57BL/6 mice were transfused into T-cell deficient Balb/c nude mice that were reconstituted with syngeneic wild-type T-cells labeled with 5-carboxyfluorescein diacetate succinimidyl ester (CFSE). After 24 hours, recipients received i.p. injection of mixture of anti-γc mAbs, or with isotype control IgG2a. The labeled T-cells were harvested from recipient spleens after 12 and 48 hours. T-cell proliferation and apoptosis were detected by flow cytometry.
  
  
  RESULTS
  T-cell proliferation was markedly inhibited and apoptotic T cells could be detected at 12 hours after the mAbs injection. Proliferation was inhibited at 48 hours, but the proportion of apoptotic T-cells was not more than at 12 hours. In the control group, however, T-cells actively proliferated and no significant apoptosis was detected at either time point.
  
  
  CONCLUSIONS
  The results suggested that blockade of γc signals can synergize with donor splenocyte transfusion and lead to inhibition of antigen-specific T-cell proliferation and induction of apoptotic T-cell death. This protocol may develop a novel approach to induce donor-specific tolerance.
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors: Qi
authors: Q
authors: Zhou
authors: Sheng
authors: S
authors: Chang
authors: Xing-Guang
authors: XG
authors: Lin
authors: Fu-Li
authors: FL
authors: Xiang
authors: Zhong-Hua
authors: ZH
authors: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005434:Flow Cytometry; D005452:Fluoresceins; D007108:Immune Tolerance / Q000187:drug effects*; D053631:Interleukin Receptor Common gamma Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology*; D013388:Succinimides; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects*
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000911:Antibodies, Monoclonal; D005452:Fluoresceins; D053631:Interleukin Receptor Common gamma Subunit; D013388:Succinimides