CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats
CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats
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DOI：
10.1007/s10157-010-0370-4
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发表时间：
2011-02-01
影响因子：
2.3
通讯作者：
Isaka, Yoshitaka
中科院分区：
文献类型：
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作者：
Miyasato, Kenro;Takabatake, Yoshitsugu;Isaka, Yoshitaka
自然产生的调节性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中的作用尚不清楚，系膜增生性肾小球肾炎是慢性肾脏疾病的主要原因。超激动型CD28特异性单抗(CD28SA)是一种高效的Treg激活剂。为了证实我们的假设，即CD28SA可减轻实验性肾小球肾炎的严重程度，用CD28SA或生理盐水治疗抗Thy1肾炎模型大鼠。CD28SA显著抑制蛋白尿和血肌酐水平的升高。经CD28SA处理的肾炎大鼠肾小球Treg表达增加，并伴有CD163阳性巨噬细胞(“交替激活”的巨噬细胞)的浸润。此外，CD28SA可显著诱导肾小球IL-10mRNA的表达，从而改善肾小球系膜细胞的增殖和细胞外基质的扩张，为抑制进行性肾小球肾炎提供了新的治疗途径。此入路的治疗价值值得进一步关注和临床前研究。
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.