Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8(-) and CD8(+) T cells in systemic lupus erythematosus

The production of type I (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-10, I L-13) cytokines by CD8(-) and CD8(+) T cells from systemic lupus erythemato sus (SLE) patients and normal subjects was investigated using an intracellu lar cytokine-staining technique. This flow cytometric method facilitates an alysis of both surface markers and cytoplasmic cytokines, after a short ter m (6h) culture with or without phorbol myristate acetate and ionomycin (PMA /I) stimulation. In SLE patients, more unstimulated T cells produced IL-10 in comparison with controls; other cytokines were not detected in unstimula ted cells. The percentage of IL-10-secreting T cells did not significantly increase after PMA/I stimulation of cells from SLE patients. The mean inten sity of fluorescence (MIF) of intracellular IL-4 staining was significantly higher in CD8(-) T cells of SLE patients than controls. Significantly fewe r CD8(-) and CD8(+) T cells from SLE patients secreted IFN-gamma after PMA/ I stimulation compared with controls. The MIF and percentage of IL-2, IL-5, and IL-13-secreting cell subsets were not significantly different between SLE patients and controls. These findings indicate that T cells of SLE pati ents are already stimulated to produce IL-10 in vivo, which may result in d ownregulation of IFN-gamma secreting CD8(-) and CD8(+) T cells observed fol lowing PMA/I stimulation. Thus, the population size of Th1 and Tc1 cells ar e reduced in SLE patients whereas the effector function of Th2 cells, with respect to IL-4 production, is enhanced in SLE patients. Furthermore, altho ugh the balance between Th1/Th2 and between Tc1/Tc2 is disrupted in SLE pat ients, it is significantly biased in favour of the Th2 subset only. (C) 200 1 Academic Press.