title: Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus.
abstract: TGF-beta has marked inhibitory effects on the immune system but also serves as a costimulatory factor in the development of T cells with down-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source. The objective of this study was to compare levels of constitutive, anti-CD2-induced and cytokine-regulated TGF-beta produced by blood lymphocytes from patients with systemic lupus erythematosus (SLE) in comparison with healthy controls. Using a highly sensitive and specific bioassay to assess TGF-beta, we report that unstimulated PBL from SLE patients, especially the NK cell subset, produced decreased levels of active TGF-beta. In response to anti-CD2, concentrations of active and total TGF-beta were also decreased in SLE. After learning that IL-2 and TNF-alpha enhance lymphocyte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrations. Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity.
authors.affiliation: Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ohtsuka
authors.forename: J D
authors.initials: JD
authors.lastname: Gray
authors.forename: M M
authors.initials: MM
authors.lastname: Stimmler
authors.forename: B
authors.initials: B
authors.lastname: Toro
authors.forename: D A
authors.initials: DA
authors.lastname: Horwitz
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology
chemical_list: D007074:Immunoglobulin G; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10