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- Title
A Superagonistic Monoclonal Antibody for CD28 Ameliorates Crescentic Glomerulonephritis in Wistar-Kyoto Rats.
- Authors
Takabatake, Yoshitsugu; Li, Xiao-Kang; Mizui, Masayuki; Miyasato, Kenro; Matsui, Isao; Kawada, Noritaka; Imai, Enyu; Hünig, Thomas; Takahara, Shiro; Wada, Takashi; Furuichi57,8, Kengo; Rakugi, Hiromi; Isaka, Yoshitaka
- Abstract
Regulatory T (Treg) cells play an important role in the resolution of crescentic glomerulonephritis, where a T helper 1 (Th1)- predominant immune response promotes crescent formation. Therefore, agents that increase Treg cells appear to be ideal for suppressing T-cell-mediated renal pathology. 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-induced nephritis in Wistar- Kyoto rats, one of the experimental models of crescentic glomerulonephritis. Administration of JJ316 attenuated crescent formation, proteinuria and glomerular accumulation of macrophages and CD8+ T cells. These changes were accompanied by increased infiltration of 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 glomerulonephritis. In an adoptive transfer experiment, two T-cell subsets (CD4+CD25+ and CD4+CD25- T cells) purified from spleens and lymph nodes of donor rats primed with JJ316 3 d before were inoculated into nephritic recipient rats, which recapitulated the beneficial effects of in vivo administration of JJ316. Furthermore, a single injection of JJ316 administered 3 d after disease induction completely protected nephritic rats from death for 2 months. In conclusion, we demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic glomerulonephritis, possibly due to expansion and activation of Treg cells.
- Subjects
THERAPEUTIC use of monoclonal antibodies; TREATMENT of glomerulonephritis; T cells; MACROPHAGES; LABORATORY rats
- Publication
Molecular Medicine, 2011, Vol 17, Issue 7/8, p686
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2010.00229