This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Ohtsuka, K Articles by Horwitz, D A Search for Related Content PubMed PubMed Citation Articles by Ohtsuka, K Articles by Horwitz, D A Social Bookmarking                         What's this?

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

Lupus, Vol. 8, No. 2, 95-102 (1999)
DOI: 10.1191/096120399678847498


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				V. Saxena, D. W. Lienesch, M. Zhou, R. Bommireddy, M. Azhar, T. Doetschman, and R. R. Singh Dual Roles of Immunoregulatory Cytokine TGF-{beta} in the Pathogenesis of Autoimmunity-Mediated Organ Damage J. Immunol., February 1, 2008; 180(3): 1903 - 1912. [Abstract] [Full Text] [PDF]

				S. G. Zheng, J. Wang, P. Wang, J. D. Gray, and D. A. Horwitz IL-2 Is Essential for TGF-beta to Convert Naive CD4+CD25- Cells to CD25+Foxp3+ Regulatory T Cells and for Expansion of These Cells J. Immunol., February 15, 2007; 178(4): 2018 - 2027. [Abstract] [Full Text] [PDF]

				H Schotte, P Willeke, S Rust, G Assmann, W Domschke, M Gaubitz, and B Schluter The transforming growth factor-{beta}1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus Lupus, February 1, 2003; 12(2): 86 - 92. [Abstract] [PDF]

				P. Youinou and R. Le Corre The multi-faceted role of transforming growth factor-beta in systemic lupus erythematosus Lupus, February 1, 1999; 8(2): 87 - 88. [PDF]