Transforming growth factor-beta1 inhibits vascular permeability factor release by T cells in normal subjects and in patients with minimal-change nephrotic syndrome.

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-beta (TGF-beta) 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-beta1 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-beta1 in patients with MCNS.

METHODS

To further test the effect of TGF-beta1 on concanavalin A (Con A)-induced VPF release, normal and MCNS T cells were stimulated with 5 microg/ml of Con A in the presence or absence of TGF-beta1, 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-beta1 to these cultures inhibited the release of VPF in a dose-dependent manner. The effect of TGF-beta1 on the release of VPF was specific, since a reversion was obtained with a neutralizing monoclonal antibody to human TGF-beta1.

CONCLUSION

Together, our data demonstrate that TGF-beta1 antagonizes the ability of T cells to release VPF, and suggest a role of TGF-beta1 in the pathophysiology of VPF in vitro.