Intravenous Methylprednisolone Pulse Therapy Target CD8+ Regulatory T Cell in Lupus Nephritis with Refractory Proteinuria

Abstract

We evaluated whether Intravenous methyl-prednisolone (IVMP) administration in patients with active class III/IV lupus nephritis (LN) is related to changes in CD8+FoxP3+ regulatory T (Treg) cell population, enhance CD8+Treg suppressive function in peripheral blood mononuclear cells (PBMCs) and renal tissues. Fourty patients with class III/IV lupus nephritis were treated with IVMP. PBMCs were isolated from patients before and after two weeks of IVMP. IVMP therapy significantly increased CD8+Foxp3+ Treg cells expression with intracellular IL-10 and granzyme B in PBMCs. IVMP-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation and induced CD4+CD45RO+ cell apoptosis. Histologically, a few of both CD4+FoxP3+ and CD8+FoxP3+ Treg cells in renal tissue of LN patients before IVMP by double immunohistochemical stain. CD8+FoxP3+ Treg cells increased in ten cases of follow-up renal biopsy specimens after IVMP. Difference of CD8+CD25+FoxP3+Treg cells in PBMCs before and two weeks after IVMP correlated with decrease of Δ daily urine protein and anti-ds DNA Ab titers. siRNA of FoxP3 significantly suppressed granzyme B expression and decreasing CD8+CD25+Treg cell induced CD4+CD45RO+cell apoptosis. IVMP therapy induces immunomodulatory effect partly by inducing CD8+CD25+Treg cell function, and hence may have therapeutic impact on treatment of LN.