Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Early rejection episodes are a major problem under CTLA4Ig/belatacept-based immunosuppression. We have previously shown that CTLA4Ig therapy is dependent on Tregs at low (LD) but not high doses in a murine heart transplant model. Therefore, we aimed at improving CTLA4Ig’s efficacy by increasing the number of Tregs.
*Methods: Heart transplantation was performed under chronic LD CTLA4Ig therapy, with the dosing being modelled after the clinically approved regimen. Groups of LD CTLA4Ig-treated mice (n=6-16) were either 1) transferred with 3×106 recipient Tregs early (D-1) or late (D8) ; or 2) were treated with IL2/anti-IL2 complexes (JES6-1; D-3, D-2, D-1) for in vivo Treg expansion.
*Results: Transferred (CD45.1/2-congenic) Tregs were viable and traceable in various compartments including the spleen, lymph nodes, blood and bone marrow up to 4 weeks. However, neither early nor late Treg transfer prolonged allograft survival under LD CTLA4Ig therapy. In contrast, IL2/anti-IL2 complexes significantly prolonged heart graft (MST: >100 days vs. 52.5 days compared to CTLA4Ig therapy only; p=0.006). CD80 expression on dendritic cells, which was significantly increased in CTLA4Ig-treated animals, probably as a result of decreased Treg numbers, was lowered in IL2/anti-IL2 complex-treated animals to levels observed in naïve animals.
*Conclusions: Whereas Treg transfer did not result in an improved allograft outcome, in vivo Treg expansion by using IL2/anti-IL2 complexes resulted in long-term graft survival, and was associated by normalized CD80 expression on dendritic cells. These results suggest a potential therapeutic option to improve outcome with CTLA4Ig-based immunosuppression.
To cite this abstract in AMA style:Schwarz C, Mahr B, Unger L, Pilat N, Regele H, Wekerle T. In Vivo Treg Expansion under Costimulation Blockade Targets Early Rejection and Improves Long-Term Outcome [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/in-vivo-treg-expansion-under-costimulation-blockade-targets-early-rejection-and-improves-long-term-outcome/. Accessed August 1, 2021.
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