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Division of Rheumatology and Immunology, Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033
TGF-ß 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-ß 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-ß
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-ß, we report that
unstimulated PBL from SLE patients, especially the NK cell subset,
produced decreased levels of active TGF-ß. In response to
anti-CD2, concentrations of active and total TGF-ß were also
decreased in SLE. After learning that IL-2 and TNF-
enhance
lymphocyte production of active TGF-ß, we found that the addition of
these cytokines was unable to increase active TGF-ß to normal
concentrations. Although we observed that IL-10 inhibited the
production of active TGF-ß, 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-ß and IL-2. Therefore, decreased production of
each of these cytokines in SLE could be important in the perpetuation
of B cell hyperactivity.
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