The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

Abstract

SUMMARY The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves’ disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves’ disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves’ disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves’ disease.

Antigen-specific Immunotherapy Regulates B Cell Activities in the Intestine

“…Previous reports indicate (19). Our data show that the forming antigen-IgE-CD23 complex induces the production of IL-10, an immune suppressor cytokine, by BCs; the results are in line with others' findings in different study systems, such as Uchimura et al indicate that T cell-derived IL-4 can activate CD23-bearing cells to overproduce IL-10 that may play an important role in Graves disease (20). Our data also indicate that the engagement of CD23 by specific antigens at lower doses increases the production of IL-10 by BCs that further inhibits the ongoing antigen-specific Th2 responses.…”

The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review

“…CD8+ cells may suppress the activation B cells via a CD40 pathway to decrease CD23+ cells and production of IL-10. Moreover, CD8+ T cells may have an effect on the correction of the Th1/Th2 balance by reducing Th2 dominance (110, 111). However, it should be verified in other study of vivo and vitro in future.…”

The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: Back to the future

“…Additionally, a polymorphism in the 3 0 UTR of hCD154, that is associated with systemic lupus erythematosus, serves to cause a more prolonged protein expression in activated lymphocytes of patients versus those in controls [97]. Moreover, it has been demonstrated that B-cell activation via a CD40 pathway leads to the over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance [98]. In terms of contribution to Graves' disease etiology, CD40 could conceivably represent a trigger to autoimmunity in an autoreactive B-cell.…”