Nanoparticles Engineered as Artificial Antigen-Presenting Cells Induce Human CD4
| Autor: | Sophia, Giang, David A, Horwitz, Sean, Bickerton, Antonio, La Cava |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
immune tolerance
T regulatory cells Immunology T cells Antigen-Presenting Cells Graft vs Host Disease Mice SCID CD8-Positive T-Lymphocytes Proof of Concept Study T-Lymphocytes Regulatory Polylactic Acid-Polyglycolic Acid Copolymer systemic lupus erythematosus Mice Inbred NOD Transforming Growth Factor beta graft-versus-host disease Animals Humans Cells Cultured Cell Proliferation Original Research autoimmunity Cell Differentiation Forkhead Transcription Factors Disease Models Animal humanized mice Leukocytes Mononuclear Interleukin-2 Nanoparticles |
| Zdroj: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro. This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-β for a paracrine release to T cells. We document that these aAPCs can induce both human CD4+ and CD8+ T cells to become FoxP3+ T regulatory cells (Tregs). The aAPC NP-expanded human Tregs are functional in vitro and can modulate systemic autoimmunity in vivo in humanized NSG mice. These findings establish a proof-of-concept to use PLGA NPs as aAPCs for the induction of human Tregs in vitro and in vivo, highlighting the immunotherapeutic potential of this targeted approach to repair IL-2 and/or TGF-β defects documented in certain autoimmune diseases such as systemic lupus erythematosus. |
| Databáze: | OpenAIRE |
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