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Suppression of Murine Lupus by <scp>CD</scp> 4+ and <scp>CD</scp> 8+ Treg Cells Induced by T Cell–Targeted Nanoparticles Loaded With Interleukin‐2 and Transforming Growth Factor β

Suppression of Murine Lupus by <scp>CD</scp> 4+ and <scp>CD</scp> 8+ Treg Cells Induced by T Cell–Targeted Nanoparticles Loaded With Interleukin‐2 and Transforming Growth Factor β

Authors :
Sean Bickerton
David A. Horwitz
Antonio La Cava
Michael Koss
Tarek M. Fahmy
Source :
Arthritis & Rheumatology. 71:632-640
Publication Year :
2019
Publisher :
Wiley, 2019.

Abstract

Objective To develop a nanoparticle (NP) platform that can expand both CD4+ and CD8+ Treg cells in vivo for the suppression of autoimmune responses in systemic lupus erythematosus (SLE). Methods Poly(lactic-co-glycolic acid) (PLGA) NPs encapsulating interleukin-2 (IL-2) and transforming growth factor β (TGFβ) were coated with anti-CD2/CD4 antibodies and administered to mice with lupus-like disease induced by the transfer of DBA/2 T cells into (C57BL/6 &#215; DBA/2)F1 (BDF1) mice. The peripheral frequency of Treg cells was monitored ex vivo by flow cytometry. Disease progression was assessed by measuring serum anti-double-stranded DNA antibody levels by enzyme-linked immunosorbent assay. Kidney disease was defined as the presence of proteinuria or renal histopathologic features. Results Anti-CD2/CD4 antibody-coated, but not noncoated, NPs encapsulating IL-2 and TGFβ induced CD4+ and CD8+ FoxP3+ Treg cells in vitro. The optimal dosing regimen of NPs for expansion of CD4+ and CD8+ Treg cells was determined in in vivo studies in mice without lupus and then tested in BDF1 mice with lupus. The administration of anti-CD2/CD4 antibody-coated NPs encapsulating IL-2 and TGFβ resulted in the expansion of CD4+ and CD8+ Treg cells, a marked suppression of anti-DNA antibody production, and reduced renal disease. Conclusion This study shows for the first time that T cell-targeted PLGA NPs encapsulating IL-2 and TGFβ can expand both CD4+ and CD8+ Treg cells in vivo and suppress murine lupus. This approach, which enables the expansion of Treg cells in vivo and inhibits pathogenic immune responses in SLE, could represent a potential new therapeutic modality in autoimmune conditions characterized by impaired Treg cell function associated with IL-2 deficiency.

Details

ISSN :
23265205 and 23265191
Volume :
71
Database :
OpenAIRE
Journal :
Arthritis & Rheumatology
Accession number :
edsair.doi...........2c17c1281f6c6a7b112318def3be5199
Full Text :
https://doi.org/10.1002/art.40773