Th17 cell inhibition in a costimulation blockade‐based regimen for vascularized composite allotransplantation using a nonhuman primate model. (5th May 2020)

• Record Type: Journal Article
• Authors: Atia, Andrew; Moris, Dimitrios; McRae, MacKenzie; Song, Mingqing; Stempora, Linda; Leopardi, Francis; Williams, Kyha; Kwun, Jean; Parker, William; Cardones, Adela R.; Kirk, Allan D.; Cendales, Linda C.
• Is Part Of: Transplant international. Volume 33:Number 10(2020)
• Page Start: 1294
• Page End: 1301
• Publication Date: 2020-05-05
• Subjects: nonhuman primates -- Th17 cells -- vascular composite allograft; Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.13612
• Languages: English
• ISSNs: 0934-0874

Abstract

Summary: Vascularized composite allotransplantation (VCA) is challenged by the morbidity of immunosuppression required to prevent rejection. The use of highly specific biologics has not been well explored in VCA. Given that psoriasis is T‐cell mediated, as is rejection of skin‐containing VCAs, we sought to assess the role of ustekinumab and secukinumab, which are approved to treat psoriasis by inhibiting Th17 cells. We combined these agents with belatacept and steroids in a VCA nonhuman primate model. Group I consisted of belatacept and steroids, group II was belatacept, ustekinumab with steroid taper, and group III was belatacept, secukinumab with steroid taper. Three animals were transplanted in each group. In group I, the mean graft survival time until the first sign of rejection was 10 days whereas in group II and III it was 10.33 and 11 days, respectively. The immunohistochemistry analysis showed that the number of IL‐17a + cells and the intensity of IL‐17a expression were significantly reduced in both dermis and hypodermis parts in groups II and III when compared to group I ( P < 0.01). Ustekinumab and secukinumab led to less T‐cell infiltration and IL‐17a expression in the allograft but provided no benefit to belatacept and steroids in VCA survival.