Production of IL-10 and IL-12 in CD40 and interleukin 4-activated mononuclear cells from patients with Graves' disease

We investigated the effect of T cell-dependent B cell activation on the pro duction of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) ob tained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subjec t groups, with a combination of anti-CD40 monoclonal antibodies and interle ukin 4 (IL-4)-activated B cells, as shown by an increased level of soluble CD23, There was also a notable increase in the number of CD23(+) cells in P BMCs from patients with Graves' disease as compared to the other subject gr oups. This combination of B cell stimulants increased production of IL-10 i n PBMCs obtained from patients with Graves' disease relative to those patie nts with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal I L-12 level. In subjects with a low basal IL-12 level there was a positive c orrelation between the production of IL-12 and that of IL-10 from PBMCs sti mulated with anti-CD40 antibodies plus IL-4, On the contrary, in the patien ts with a high basal IL-12 level, no change or a decrease of IL-12 producti on was observed after the stimulation. Thus, T cell-dependent B cell activa tion via a CD40 pathway triggers the overproduction of IL-10 and overcome t he effect of IL-12 to shift the Th-1/Th-2 balance to Th-2 dominance in pati ents with Graves' disease but not in Hashimoto's thyroiditis or type 1 diab etes. (C) 2000 Academic Press.