Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Clin Exp Nephrol. 2011 Feb;15(1):50-7. doi: 10.1007/s10157-010-0370-4. Epub 2010 Nov 16.
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.
To confirm our hypothesis that CD28SA reduces the severity of experimental glomerulonephritis, anti-Thy1 nephritis model rats were treated with CD28SA or saline.
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.
We established a new therapeutic approach to suppressing progressive glomerulonephritis. The therapeutic value of this approach warrants further attention and preclinical studies.
天然存在的调节性 T 细胞（Treg）对于预防自身免疫和对病原体的过度免疫反应至关重要；然而，Treg 在系膜增生性肾小球肾炎（导致慢性肾脏病的主要原因之一）中的作用尚不清楚。超激动型 CD28 特异性单克隆抗体（CD28SA）是大鼠中 Treg 的高效激活剂。
为了证实我们的假设，即 CD28SA 可降低实验性肾小球肾炎的严重程度，用 CD28SA 或生理盐水处理抗 Thy1 肾炎模型大鼠。
CD28SA 显著抑制蛋白尿和血清肌酐水平的升高。用 CD28SA 治疗的肾炎大鼠的肾小球中 Treg 浸润增加，同时浸润 CD163 阳性巨噬细胞（“替代激活”巨噬细胞）。此外，CD28SA 可显著诱导肾小球中白细胞介素-10 mRNA 的表达，从而改善系膜细胞增殖和细胞外基质扩张。
我们建立了一种抑制进行性肾小球肾炎的新治疗方法。该方法的治疗价值值得进一步关注和临床前研究。
