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Cytokine-mediated down-regulation of B cell activity in SLE: effects of interleukin-2 and transforming growth factor-beta

J D Gray

F P Quismorio, Jr

W Lee

University of Southern California School of Medicine, Department of Medicine, Division of Rheumatology and Immunology, Los Angeles, USA

D A Horwitz

University of Southern California School of Medicine, Department of Medicine, Division of Rheumatology and Immunology, Los Angeles, USA; University of Southern California School of Medicine, Division of Rheumatology and Immunology, 2011 Zonal, Ave. HMR-711, Los Angeles, CA 90033, USA

We have recently reported that transforming growth factor-beta (TGF-b) co-stimulates interleukin-2 (IL-2) activated CD8/ T cells to down-regulate antibody production. In SLE, lymphocyte production of both IL-2 and TGF-b is decreased. Here we report that a brief treatment of PBMC from SLE patients with IL-2 and TGF-b can result in marked inhibition of spontaneous polyclonal IgG and autoantibody production. Peripheral blood mononuclear cells (PBMC) from 12 patients with active SLE were exposed to IL-2 with or without TGF-b for three days, washed and cultured for seven more days. The mean decrease in IgG secretion was 79%. The strongest inhibitory effect was observed in cases with the most marked B cell hyperactivity. Spontaneous production of anti-nucleoprotein (NP) antibodies was observed in four cases and cytokine treatment of PBMC decreased autoantibody production by 50–96%. IL-2 inhibited Ig production by either TGF-b-dependent or independent mechanisms in individual patients. In a study of anti-CD2 stimulated IgG production in a patient with active SLE, we documented that IL-2 and TGF-b reversed the enhancing effects of CD8/ T cells on IgG production and induced suppressive activity instead. These results raise the possibility that cytokine-mediated down-regulation of B cell hyperactivity in SLE may have therapeutic potential.

Key Words: cytokines • systemic lupuserythematosus • transforming growth factor-beta • interleukin-2 • B lymphocytes

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