The Ratio And Time Effect: Administration Of Il-2-anti-il-2 Complexes Controls Vascularized Composite Allograft Survival.
Heng Xu, M.D.1, L. Scott Levin, M.D., FACS.2.
1Shanghai Ninth People's Hospital, Shanghai, China, 2Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
PURPOSE: Vascularized composite allograft (VCA) transplantation is a novel transplantation. The interplay between Treg and CD4+ effector, CD8+ T cells is important for allograft acceptance. In this study, we explored and compared the benefits of pre- and post-Tx IL-2C administrations.
METHODS: We performed the VCA model utilizing Balb/c mice as donor and C57bl/10 mice as recipient. Mice were divided randomly to 6 groups (n=15/group). Group A: control; Group B: post-Tx. IL-2C (inj. POD 0, 1, 2); Group C: Rapamycin (2mg/kg, 28days); Group D: Rapamycin plus post-Tx. IL-2C; Group E: pre-Tx. IL-2C (POD -5, -4, -3); Group F: Rapamycin plus pre-Tx. IL-2C. Signs of allograft rejection were monitored daily. General and local inflammation were assessed using flow-cytometry, qPCR and histopathology analysis.
RESULTS: Both pre- and post-Tx. IL-2C administrations prolong VCA survival (p<0.001) by expanding the Treg number-5 folds than control (p<0.001), but pre-Tx. IL-2C administration significantly increased survival compared to post-Tx (p<0.01), due to (1) lower IFN-γ+ CD4+ effector and CD8+ T cells. (2) lower Ki67+ CD4+ effector and CD8+ T cells. (3) increased ratio of Treg to CD8+ T cells. The histopathology analysis supports these results.
CONCLUSION: This is the first detailed research of pre-Tx IL-2C administration. We believe that preconditioning IL-2C strategy can be used clinically and contribute to transplantation tolerance further.
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