IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against Proteinuric CKD

Tania Polhill, Geoff Yu Zhang, Min Hu, Andrew Sawyer, Jimmy Jianheng Zhou, Mitsuru Saito, Kylie E. Webster, Ya Wang, Yiping Wang, Shane T. Grey, Jonathan Sprent, David C. H. Harris, Stephen I. Alexander*, Yuan Min Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease.

Original languageEnglish
Pages (from-to)1303-1308
Number of pages6
JournalJournal of the American Society of Nephrology
Volume23
Issue number8
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

Keywords

  • VERSUS-HOST-DISEASE
  • IN-VIVO EXPANSION
  • MONOCLONAL-ANTIBODY
  • AUTOIMMUNE-DISEASE
  • CUTTING EDGE
  • IMMUNOTHERAPY
  • IL-2
  • INTERLEUKIN-2
  • TOLERANCE
  • CANCER

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