Transforming Growth Factor-β ₁ Inhibits Vascular Permeability Factor Release by T Cells in Normal Subjects and in Patients with Minimal-Change Nephrotic Syndrome

Abstract

Background/Aim: A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS). Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that inhibits proliferation, cytokine production, and cytotoxic activity of T cells and natural killer cells. We, therefore, investigated the effects of TGF-β₁ on the release of VPF by peripheral blood T cells from MCNS patients. The aim of our study was to determine the in vitro immunosuppressive capacity of TGF-β₁ in patients with MCNS. Methods: To further test the effect of TGF-β₁ on concanavalin A (Con A)-induced VPF release, normal and MCNS T cells were stimulated with 5 µg/ml of Con A in the presence or absence of TGF-β₁, and the culture supernatants were tested for the presence of VPF by the method of Lagrue et al. The disease controls included 16 patients with IgA nephropathy. Results: Significantly increased spontaneous and Con A-stimulated secretion of VPF was detected in T-cell cultures of MCNS patients with the nephrotic syndrome as compared with those of normal controls. Addition of TGF-β₁ to these cultures inhibited the release of VPF in a dose-dependent manner. The effect of TGF-β₁ on the release of VPF was specific, since a reversion was obtained with a neutralizing monoclonal antibody to human TGF-β₁. Conclusion: Together, our data demonstrate that TGF-β₁ antagonizes the ability of T cells to release VPF, and suggest a role of TGF-β₁ in the pathophysiology of VPF in vitro.