We have developed a “color-coded” adoptive transfer model for T cell subset identification that enables serial analysis of islet allograft infiltrating yellow induced regulatory T cells (iTreg), green natural regulatory T cells (nTreg) and red effector T cells (Teff) in live animals using endoscopic confocal microscopy (Nat Med. 2010). While numerous studies have indicated that IL-17 and /TH17 cells play an important role in allograft rejection, there are also studies suggest otherwise. We now report in vivo imaging serial studies based on islet allograft transplantation performed in Foxp3-RFP x RORγt-eGFP double indicator mice recipient. Interaction and conversion between Treg and Th17 cells are investigated. Additionally, the balance between Treg and TH17 cells was tilted upon IL-6 infusion via slow-releasing osmotic pump, which was also associated with accelerated rejection. Our data indicates that CD3+CD4+RORγt+TH17 cells do not play a critical role in medicating islet allograft rejection. Whatmore, TH17 phenotype seems to be transient during the course of allograft response, and the appearance of Th17 cells depends on the pre-presence of other types of RORγt+ Non-TH17 cells and a protracted inflammatory melieu. The IL-6 triggered accelerated allograft rejection is associated with inhibition of conversion of naive CD4+ T cells to iTreg as well as the loss of nTreg phenotype. Additionally, the accelerated rejection could not be prevented by anti-CD154 mAb plus Rapamycin, a strong tolerizing regimen that promotes iTreg conversion and nTreg stability in hosts not receiving IL-6 treatment. The data supports the the idea that selective anti-inflammatory treatment may be imperative for induction and maintenance of allograft tolerance, especially in complex clinical situations where inflammation plays a significant role.

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