Vascularized composite allografts (VCA) are a novel, life-enhancing form of transplantation (Tx). The complexity of host immune responses to VCA tissues, especially those involving skin, is only gradually being unraveled. In particular, while the interplay between T-regulatory (Treg) cells and CD4 and CD8 effector T cells is considered of central importance in determining the acceptance of rejection of solid organ allografts, there is little information concerning the contribution of Tregs to VCA survival. In this study, a mouse forelimb orthotopic Tx model utilizing Balb/c mice as donor and C57bl/10 mice as recipient was set up. We explored the benefits of pre- and post-Tx IL-2/anti-IL-2 complex (IL-2C) administration as a means to promote Treg-dependent allograft survival. Both strategies expanded the Treg population in vivo and prolonged VCA survival (p<0.001), but IL-2C administration pre-Tx led to significantly increased survival compared to IL-2C administration post-Tx (p<0.01). In addition, compared to post-Tx therapy, pre-Tx therapy resulted in an increased ratio of Tregs to CD8+ T cells (p<0.001)(Figure 2), reduced proliferation of CD4 and CD8 effector T cells, and reduced production of IFN-γ. In summary, our studies involving different IL-2C-mediated Treg expansion strategies showed that pre-Tx IL-2C therapy may be a useful component of developing strategies to promote VCA survival.

CITATION INFORMATION: Xu H, Dahiya S, Wang L, Akimova T, Hancock W, Levin S. Utility of IL-2 Complexes in Promoting Vascularized Composite Allograft Survival. Am J Transplant. 2017;17 (suppl 3).

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