免疫学
抗原
旁观者效应
免疫系统
1型糖尿病
过继性细胞移植
抗原呈递
T细胞
医学
CD8型
生物
糖尿病
内分泌学
作者
Colin J Raposo,Judith D Cserny,Gloria Serena,Jonathan Chow,Patricia Cho,Hanyang Liu,David Kotler,Armon Sharei,Howard Bernstein,Shinu John
标识
DOI:10.3389/fimmu.2022.869669
摘要
Antigen-specific therapies that suppress autoreactive T cells without inducing systemic immunosuppression are a much-needed treatment for autoimmune diseases, yet effective strategies remain elusive. We describe a microfluidic Cell Squeeze® technology to engineer red blood cells (RBCs) encapsulating antigens to generate tolerizing antigen carriers (TACs). TACs exploit the natural route of RBC clearance enabling tolerogenic presentation of antigens. TAC treatment led to antigen-specific T cell tolerance towards exogenous and autoantigens in immunization and adoptive transfer mouse models of type 1 diabetes (T1D), respectively. Notably, in several accelerated models of T1D, TACs prevented hyperglycemia by blunting effector functions of pathogenic T cells, particularly in the pancreas. Mechanistically, TACs led to impaired trafficking of diabetogenic T cells to the pancreas, induced deletion of autoreactive CD8 T cells and expanded antigen specific Tregs that exerted bystander suppression. Our results highlight TACs as a novel approach for reinstating immune tolerance in CD4 and CD8 mediated autoimmune diseases.
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