Abstract

Expression and immunological significance of IFN-gamma, a pivotal cytokine in murine lupus, have not been clearly demonstrated in human systemic lupus erythematosus (SLE). In the present study we investigated the expression of IFN-gamma in peripheral blood T cells from patients with SLE and its role in the production of the soluble B lymphocyte stimulator (sBLyS). Peripheral blood T cells from patients with SLE expressed significantly larger amounts of IFN-gamma in response to stimulation with anti-CD3 mAb plus anti-CD28 mAb than those from normal controls as shown by three analytical methods, including ELISA, flow cytometry, and quantitative RT-PCR. The ratio of IFN-gamma-producing T cells to effector memory T cells in CD3(+)CD4(+) and CD3(+)CD8(+) populations in patients with SLE was significantly higher than that of normal controls. The T-box expressed in T cells (T-bet) mRNA/GATA-binding protein-3 (GATA-3) mRNA ratio was significantly higher in patients with SLE than in normal controls. T cell culture supernatants from patients with SLE contained significantly higher sBLyS-inducing activity than normal controls; this was almost completely inhibited by the addition of anti-human IFN-gamma mAb. Percentages of BLyS-expressing peripheral blood monocytes in patients with SLE were significantly higher than those of normal controls. Monocytes from patients with SLE produced significantly larger amounts of sBLyS in response to IFN-gamma than those from normal controls. Taken together, these data strongly indicate that the overexpression of IFN-gamma in peripheral blood T cells contributes to the immunopathogenesis of SLE via the induction of sBLyS by monocytes/macrophages, which would promote B cell activation and maturation.

Highlights

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  • In the present study we investigated the expression of IFN-␥ in peripheral blood T cells from patients with systemic lupus erythematosus (SLE) and its role in the production of the soluble B lymphocyte stimulator

  • In the present study we demonstrated the following: 1) peripheral blood T cells from patients with SLE expressed significantly larger amounts of IFN-␥ in response to CD28 costimulation than those from normal controls; 2) overexpressed IFN-␥ contributed to the excessive soluble B lymphocyte stimulator (sBLyS)-inducing activity in T cell culture supernatants of patients with SLE; and 3) monocytes from patients with SLE produced significantly larger amounts of sBLyS in response to the stimulation with rhIFN-␥ than those from normal controls

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Summary

Introduction

Peripheral blood T cells from patients with SLE expressed significantly larger amounts of IFN-␥ in response to stimulation with anti-CD3 mAb plus anti-CD28 mAb than those from normal controls as shown by three analytical methods, including ELISA, flow cytometry, and quantitative RT-PCR. We recently demonstrated that peripheral blood T cells from patients with SLE produced significantly larger amounts of IFN-␥ protein in response to anti-CD3 mAb plus anti-inducible costimulator mAb stimulation [13].

Results
Conclusion

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