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

我们假设，CD 28的超激动性单克隆抗体，JJ 316，这已被称为优先扩大Treg细胞在体内，可以防止肾毒性血清（NTS）诱导的肾炎在Wistar-Kyoto大鼠。施用JJ 316减弱了新月体形成、蛋白尿和巨噬细胞和Treg细胞的肾小球积累。在肾小球巨噬细胞中，治疗后CD 163+亚群显著增加，表明Treg细胞可能调节巨噬细胞的表型，导致GN消退。连续转移实验概括了体内施用JJ 316的有益效果。此外，在疾病诱导后3天单次注射JJ 316完全保护肾炎大鼠免于死亡2个月。总之，我们已经证明用JJ 316治疗对实验性新月体GN具有显著的治疗效果，这可能是由于Treg细胞的扩增。

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.