Original Article

Clinical and Experimental Nephrology

, Volume 15, Issue 1, pp 50-57

CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats

  • Kenro MiyasatoAffiliated withDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine
  • , Yoshitsugu TakabatakeAffiliated withDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine
  • , Junya KaimoriAffiliated withDepartment of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine
  • , Tomonori KimuraAffiliated withDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine
  • , Harumi KitamuraAffiliated withDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine
  • , Hiroshi KawachiAffiliated withDepartment of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences
  • , Xiao-Kang LiAffiliated withLaboratory of Transplantation Immunology, National Research Institute for Child Health and Development
  • , Thomas HünigAffiliated withInstitut für Virologie and Immunobiologie, Universtät Würzburg
  • , Shiro TakaharaAffiliated withDepartment of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine
    • , Hiromi RakugiAffiliated withDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine
    • , Yoshitaka IsakaAffiliated withDepartment of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine Email author 

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Abstract

Background

Naturally occurring regulatory T cells (Treg) are essential for the prevention of autoimmunity and overshooting immune responses to pathogens; however, the involvement of Treg in mesangioproliferative glomerulonephritis, a major cause of chronic kidney disease, remains unclear. Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of Treg in rats.

Method

To confirm our hypothesis that CD28SA reduces the severity of experimental glomerulonephritis, anti-Thy1 nephritis model rats were treated with CD28SA or saline.

Results

CD28SA significantly suppressed the increase in proteinuria and serum creatinine levels. CD28SA-treated nephritic rats exhibited an increase in the infiltration of Treg in the glomeruli accompanied by infiltration of CD163-positive macrophages (“alternatively activated” macrophages). In addition, CD28SA significantly induced interleukin-10 mRNA expression in glomeruli, thereby ameliorating mesangial cell proliferation and extracellular matrix expansion.

Conclusion

We established a new therapeutic approach to suppressing progressive glomerulonephritis. The therapeutic value of this approach warrants further attention and preclinical studies.

Keywords

CD28 Regulatory T cell FoxP3 “Alternatively activated” macrophage