Departments of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan ; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Division of Pediatric Nephrology, China Medical University Hospital, Taichung, Taiwan.
PLoS One. 2014 Jan 27;9(1):e81344. doi: 10.1371/journal.pone.0081344. eCollection 2014.
We focus on the role of CD8(+) Treg cell in Intravenous methyl-prednisolone (IVMP) pulse therapy in forty patients with active Class III/IV childhood lupus nephritis (LN) with heavy proteinuria. IVMP therapy for five days. From peripheral blood mononuclear cells (PBMCs) and renal tissues, we saw IVMP therapy definitely restoring both CD4(+)CD25(+)FoxP3(+) and CD8(+)CD25(+)Foxp3(+) Treg cell number plus greater expression with intracellular IL-10 and granzyme B in CD8(+)FoxP3(+) Treg from PBMCs. IVMP-treated CD8(+)CD25(+) Treg cells directly suppressed CD4(+) T proliferation and induced CD4(+)CD45RO(+) apoptosis. Histologically, CD4(+)FoxP3(+) as well as CD8(+)FoxP3(+) Treg cells appeared in renal tissue of LN patients before IVMP by double immunohistochemical stain. CD8(+)FoxP3(+) Treg cells increased in 10 follow-up renal biopsy specimens after IVMP. Reverse correlation of serum anti-C1q antibody and FoxP3(+) Treg cells in PBMNCs (r = -0.714, P<0.01). After IVMP, serum anti-C1q antibody decrease accompanied increase of CD4(+)FoxP3(+) Treg cells. CD8(+)Treg cells reduced interferon-r response in PBMCs to major peptide autoepitopes from nucleosomes after IVMP therapy; siRNA of FoxP3 suppressed granzyme B expression while decreasing CD8(+)CD25(+)Treg-induced CD4(+)CD45RO(+) apoptosis. Renal activity of LN by SLEDAI-2k in childhood LN was significantly higher than two weeks after IVMP (P<0.01). CD8(+)FoxP3(+) Treg cells return in post-IVMP therapy and exert crucial immune modulatory effect to control autoimmune response in LN.
DMR97-IRB-259.
我们关注 CD8(+)Treg 细胞在静脉注射甲基强的松龙（IVMP）脉冲治疗中的作用，该治疗用于 40 例有大量蛋白尿的活动期 III/IV 级儿童狼疮性肾炎（LN）患者。IVMP 治疗 5 天。从外周血单核细胞（PBMC）和肾组织中，我们发现 IVMP 治疗肯定会恢复 CD4(+)CD25(+)FoxP3(+)和 CD8(+)CD25(+)Foxp3(+)Treg 细胞的数量，并增加 PBMC 中细胞内 IL-10 和颗粒酶 B 的表达。IVMP 治疗的 CD8(+)CD25(+)Treg 细胞直接抑制 CD4(+)T 细胞增殖，并诱导 CD4(+)CD45RO(+)凋亡。组织学上，在 IVMP 治疗前，LN 患者的肾组织中出现 CD4(+)FoxP3(+)和 CD8(+)FoxP3(+)Treg 细胞，双免疫组化染色。IVMP 后 10 例随访肾活检标本中 CD8(+)FoxP3(+)Treg 细胞增加。血清抗 C1q 抗体与 PBMCs 中 FoxP3(+)Treg 细胞呈负相关（r=−0.714，P<0.01）。IVMP 后，血清抗 C1q 抗体下降伴随 CD4(+)FoxP3(+)Treg 细胞增加。IVMP 治疗后，CD8(+)Treg 细胞降低 PBMCs 对核小体主要肽自身表位的干扰素-r 反应；FoxP3 的 siRNA 抑制颗粒酶 B 的表达，同时减少 CD8(+)CD25(+)Treg 诱导的 CD4(+)CD45RO(+)凋亡。儿童 LN 的 LN 活动度通过 SLEDAI-2k 在 IVMP 后两周明显升高（P<0.01）。CD8(+)FoxP3(+)Treg 细胞在 IVMP 后恢复，并发挥关键的免疫调节作用来控制 LN 中的自身免疫反应。
DMR97-IRB-259。
