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.
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.
Uchimura
K
K
Department of Internal Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan.
Itoh
M
M
Yamamoto
K
K
Imamura
S
S
Makino
M
M
Kato
T
T
Fujiwara
K
K
Sawai
Y
Y
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017455:Receptors, IgE / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D019013:CD40 Antigens; D017455:Receptors, IgE; D016753:Interleukin-10; D015847:Interleukin-4