Session Time: 2:15pm-3:45pm
Presentation Time: 2:27pm-2:39pm
Location: Room 121-C
We have previously shown that peri-transplant infusion of donor cells treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI) in combination with peri-transplant anti-CD20 and rapamycin induce permanent porcine islet xenograft survival in mice. Mechanisms of protection by the tripatite therapy remain unclear. Methods: ECDI-treated porcine splenocytes (SP) were infused to B6 mice at day -7, +1. Anti-CD20 (250 μg) was given on day -10, +1. Rapamycin (1mg/kg daily) was given from day -7 to +10. 3000 IEQ of porcine islets were transplanted in B6 mice on day 0. Delayed-type hypersensitivity (DTH) assay and donor-stimulated cytokine production by ELISPOT were assessed. Untreated mice were controls. Results: In controls, a heightened DTH response to porcine cell challenge was observed. Surprisingly, recipient T cells exhibited a robust IL-17 response to indirect donor stimulation, and to a lesser extent to direct donor stimulation. In comparison, only a moderate IFN-γ response was observed and only to indirect donor stimulation. In contrast, donor ECDI-SP alone significantly reduced DTH response to ∼50%, as well as the indirect and direct IL-17 responses (∼30% and 50%, respectively). However, donor ECDI-SP alone significantly augmented the indirect IFN-γ response by ∼10 fold. When ECDI-SP was further combined with anti-CD20 and rapamycin, the IFN-γ response was completely suppressed, and a further reduction of IL-17 responses was observed (both to ∼20% of control), correlating with islet xenograft protection. Conclusions: Pig-to-mouse islet transplantation induces robust IL-17 responses in addition to IFN-γ responses. Donor ECDI-SP effectively suppresses anti-donor IL-17 responses, and in combination with anti-CD20 and rapamycin further suppresses anti-donor IFN-γ response, resulting in permanent islet xenograft protection. The current study elucidates a unique role of donor ECDI-SP in controlling anti-xenogeneic IL-17 responses, likely an important barrier to xenograft survival.
To cite this abstract in AMA style:Kang H, Wang S, Zhang X, Zhang L, Miller S, Hering B, Luo X. Effective Control of Anti-Xenogeneic IL-17 Response for Tolerance Induction in Xenogeneic Islet Cell Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/effective-control-of-anti-xenogeneic-il-17-response-for-tolerance-induction-in-xenogeneic-islet-cell-transplantation/. Accessed December 12, 2019.
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