CD4+ T helper cells and regulatory T cells in active lupus nephritis: an imbalance towards a predominant Th1 response?

Abstract

The objective of this study was to evaluate the frequency of CD4⁺ T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (T_reg) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients. T cell subtypes in PBMC were re-evaluated at 6 months of therapy. CD4⁺ T cells were decreased in PBMC in LN compared with DC and HC (P = 0·0001). No differences were observed in urinary CD4⁺ T cell subsets between LN and DC. The frequency of urinary Th17 cells was higher in patients with non-proliferative than in proliferative LN (P = 0·041). CD3⁺ and T-box 21 ( {\mathrm{T}}_{\text{bet}}^{+} ) cells were found in glomeruli and interstitium of LN patients, while forkhead box protein 3 (FoxP3), retinoid-related orphan receptor gamma (ROR-γ) and GATA binding protein 3 (GATA-3) were present only in glomeruli. Th1 cells in PBMC were correlated negatively with urinary Th1 cells (Rho = –0·531; P = 0·028) and with T_bet in renal interstitium (Rho = –0·782; P = 0·004). At 6 months, LN patients showed an increase in Th17 cells in PBMC. In conclusion, the inverse association between Th1 cells from PBMC and urinary/renal tissue indicate a role for Th1 in LN pathophysiology. Urinary Th17 cells were associated with less severe LN, and Th17 increased in PBMC during therapy. Urinary CD4⁺ T cells were not different between LN and DC.