Effective Control of Anti-Xenogeneic IL-17 Response for Tolerance Induction in Xenogeneic Islet Cell Transplantation
1Medicine, Northwestern University Feinberg school of Medicine, Chicago, IL
2Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China
3Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
4Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL
5Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN.
Meeting: 2015 American Transplant Congress
Abstract number: 364
Keywords: Indirect pathway, Interferon (IFN), Islets, Xenotransplantation
Session Information
Session Name: Concurrent Session: Islet Transplantation: Basic
Session Type: Concurrent Session
Date: Tuesday, May 5, 2015
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 May 21, 2025.« Back to 2015 American Transplant Congress