Therapeutic effect of CD28 superagonist on renal disease via expansion of regulatory T cells

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: TAKABATAKE Yoshitsugu 大阪大学, 医学系・研究科, 助教 (30403075)
• Co-Investigator(Kenkyū-buntansha): ISAKA Yoshitaka 大阪大学, 大学院・医学研究科, 准教授 (00379166) ; IMAI Enyu 名古屋大学, 大学院・医学研究科, 特任准教授 (00223305)
• Project Period (FY): 2009 – 2011
• Keywords: CD28 / スーパーアゴニスト / 制御性T細胞 / FoxP3 / 抗GBM抗体腎炎

Research Abstract

We hypothesized that a superagonistic monoclonal antibody for CD28, JJ316, which has been known to preferentially expand Treg cells in vivo, could prevent nephrotoxic serum(NTS)-induced nephritis in Wistar-Kyoto rats. Administration of JJ316 attenuated crescent formation, proteinuria, and glomerular accumulation of macrophages and Treg cells. Among glomerular macrophages, the CD163+ subset was significantly increased after treatment, suggesting that Treg cells may modulate the phenotype of macrophages leading to resolution of GN. Adoptive transfer experiment recapitulated the beneficial effects of in vivo administration of JJ316. Furthermore a single injection of JJ316 administered 3 days after disease induction completely protected nephritic rats from death for 2 months. In conclusion, we have demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic GN, probably due to an expansion of Treg cells.

Research Products

• [Journal Article] A superagonistic monoclonal antibody for CD28 ameliorates crescentic glomerulonephritis in wistar-kyoto rats (2011)
  • Author(s): Takabatake Y, Li XK, Mizui M, Miyasato K, Matsui I, Kawada N, Imai E, Hunig T, Takahara S, Wada T, Furuichi K, Rakugi H, Isaka Y.
  • Journal Title: Mol Med Volume: 17(7-8) Pages: 686-96
  • Peer Reviewed
• [Journal Article] CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats (2011)
  • Author(s): Miyasato K, Takabatake Y, Kaimori J, Kimura T, Kitamura H, Kawachi H, Li XK, Hunig T, Takahara S, Rakugi H, Isaka Y.
  • Journal Title: Clin Exp Nephrol Volume: 15(1) Pages: 50-7
  • Peer Reviewed
• [Journal Article] CD28スーパーアゴニスト (2011)
  • Author(s): 高畠義嗣
  • Journal Title: 医学のあゆみ Volume: 237 Pages: 260-261
• [Presentation] ループス腎炎モデルマウスに対するCD28スーパーアゴニストの治療効果の検証 (2010)
  • Author(s): 高畠義嗣、木村友則、宮里研郎、高橋篤史、植畑拓也、貝森淳哉、川田典孝、今井圓裕、HunigThomas、李小康、楽木宏実、猪阪善隆
  • Organizer: 日本腎臓学会第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-16
• [Presentation] CD28スーパーアゴニストのラット半月体形成性腎炎に対する治療効果の検討 (2009)
  • Author(s): 高畠義嗣
  • Organizer: 分子腎臓研究会
  • Place of Presentation: 京都
  • Year and Date: 2009-09-05
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/kid/index.html