DECREASED PRODUCTION OF TGF-BETA BY LYMPHOCYTES FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

TGF-beta has marked inhibitory effects on the immune system but also s erves as a costimulatory factor in the development of T cells with dow n-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form, We have recently le arned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source, The objective of this s tudy was to compare levels of constitutive, anti-CD2-induced and cytok ine-regulated TGF-beta produced by blood lymphocytes from patients wit h systemic lupus erythematosus (SLE) in comparison with healthy contro ls, 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 de creased in SLE. After learning that IL-2 and TNF-alpha enhance lymphoc yte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrat ions, Although we observed that IL-10 inhibited the production of acti ve TGF-beta, antagonism of this cytokine was unable to completely corr ect the defect, In two SLE patients with B cell hyperactivity, spontan eous IgG production was almost abolished by the combination of TGF-bet a and IL-2, Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity .