Effector T cell migration to pancreatic islet allografts is dependent on donor antigen recognition and not Gai chemokine signaling. (TRAN1P.945)

• DOI: 10.4049/jimmunol.194.supp.140.27
• Publication Date: 2023-01-01T09:55:32Z
• Authors: Qianqian Zhang; Hehua Dai; Qiang Zeng; Amanda Williams; Martin Oberbarnsc...; Fadi Lakkis
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences

Abstract Host effector T cell graft infiltration is a key step in the pathogenesis of both acute and chronic rejection. Recent data indicate effector T cell migration into primary vascularized organ transplants such as heart and kidney is driven by donor antigen recognition, not via Gai-coupled chemokine receptor signaling. Whether it is true for neovascularized pancreatic islet allografts is unknown. We co-transferred pertussis toxin (Ptx)-treated and untreated TCR-tg (OT-1) effector T cells into B6 recipients 7-10 days after transplanting B6-Act-OVA or B6 islet grafts under the kidney capsule. Ptx irreversibly blocks Gai-dependent signaling. Grafts were imaged 20-24 hours after T cell transfer by two-photon intravital microscopy. We observed B6-Act-OVA grafts were heavily infiltrated with OT-1 effector T cells irrespective of pre-treatment with Ptx or not (453.7+/-170.0 vs. 632.8+/-221.1 per imaging volume, n = 10, p = 0.0522 ), while B6 grafts, which lack the cognate antigen recognized by OT-1 T cells, were free of infiltrate (<5 cells, n = 7). These results indicate that, similar to heart and kidney transplants, islet allograft infiltration with host effector T cells is driven by donor antigen, not by Gai signaling. The paradigm of antigen-driven effector T cell migration is therefore generalizable to both primary vascularized grafts, in which donor antigens are abundantly expressed on the endothelium, and neovascularized cellular grafts whereby the endothelium is of host origin.