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

We have recently reported that transforming growth factor-beta (TGF-beta) c o-stimulates interleukin-2 (IL-2) activated CD8(+) T cells to down-regulate antibody production. In SLE, lymphocyte production of both IL-2 and TGF-be ta is decreased. Here we report that a brief treatment of PBMC from SLE pat ients with IL-2 and TGF-beta can result in marked inhibition of spontaneous polyclonal IgG and autoantibody production. Peripheral blood mononuclear c ells (PBMC) from 12 patients with active SLE were exposed to IL-2 with or w ithout TGF-beta for three days, washed and cultured for seven more days. Th e mean decrease in IgG secretion was 79%. The strongest inhibitory effect w as observed in cases with the most marked B cell hyperactivity. Spontaneous production of antinucleoprotein (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-beta-dependent or independent mechanisms in individual patients. In a study of anti-CD2 stimulated IgG pr oduction in a patient with active SLE, we documented that IL-2 and TGF-beta reversed the enhancing effects of CD8(+) T cells on IgG production and ind uced suppressive activity instead. These results raise the possibility that cytokine-mediated down-regulation of B cell hyperactivity in SLE may have therapeutic potential.