Local control of T cell fate in lymph nodes safely and durably reverses myelin-driven autoimmunity
Year: 2025
Type: article
Abstract: Development of tolerogenic, antigen-specific immunotherapies could overcome limitations of existing treatments for inflammatory autoimmune diseases by achieving potent, durable remission without impacting healthy immune surveillance. Here, we deliver diffusion-limited polymer depots to lymph nodes to locally guide T cell fates for the treatment of multiple sclerosis (MS), an autoimmune disease that occurs when the immune system mistakenly attacks myelin. In preclinical MS models, depots loaded with myelin self-antigen and tolerizing cues mediate localized retention of activated CD4 T cells, promote myelin-specific regulatory T cells, and reshape inflammation in the central nervous system (CNS) to eliminate lesions. Selective disease reversal is achieved with a single treatment that induces long-lasting remission without hindering healthy responses to vaccine challenge with foreign antigen. Furthermore, depots offer favorable chemistry and manufacturing control features and are well tolerated in non-human primates. This work supports a clinically feasible concept for inducing safe, effective, antigen-specific tolerance without systemic or repeated dosing.
Authors: Senta M. Kapnick, Emily A. Gosselin, Shannon J. Tsai, Robert S. Oakes, Zahra A. Habibabady, Marian A. Ackun-Farmmer, Sean T. Carey, Shrey A. Shah, Ruochen Shen, Eugene Froimchuk, Haleigh B. Eppler, Christopher J. Bridgeman, Alexis A. Yanes, Ryan A. McIlvaine, Maeesha Noshin, Lisa H. Tostanoski, Sheneil K. Black, Xiangbin Zeng, Agnes Azimzadeh, Richard N. Pierson, Jonathan S. Bromberg, Christopher M. Jewell
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: National Science Foundation, U.S. Department of Veterans Affairs, Massachusetts General Hospital, University of Maryland, National Institutes of Health, A. James Clark School of Engineering, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1309936681, G1886068547, G1922133794, G1953755467, G219369639, G2354209684, G3014393894, G3190688598, G3582644764, Harnessing biomaterials to study the link between local lymph node function and systemic tolerance, G4056947026, G4563812999, G5002882618, Graduate Research Fellowship Program (GRFP), Graduate Research Fellowship Program (GRFP), G6817353502, G7660896353, G7662339094, G8193659649, G8496449571, G8658026990, G9000043856, G9000091092, G9000111216, G9000186205, G9000188169, G9000202609, G9000213785, G9000277237, G9000333792, G9000337132, Defining the induction and maintenance of myelin-specific tolerance in T cells and B cells using local lymph node depots, Regulatory T Cells and Lymphatic Endothelial Cells: Regulatory Interactions for Migration and Suppression, Training Grant in Cancer Biology, G970892991
OpenAlex ID: W4415823571