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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.   Trial Registration    DMR97-IRB-259

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CD8+ Treg Cells Associated with Decreasing Disease Activity after Intravenous Methylprednisolone Pulse Therapy in Lupus Nephritis with Heavy Proteinuria