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 production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subject groups, with a combination of anti-CD40 monoclonal antibodies and interleukin 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 PBMCs from patients with Graves' disease as compared to the other subject groups. This combination of B cell stimulants increased production of IL-10 in PBMCs obtained from patients with Graves' disease relative to those patients with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal IL-12 level. In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. On the contrary, in the patients with a high basal IL-12 level, no change or a decrease of IL-12 production was observed after the stimulation. Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes.
Itoh
M
M
Department of Internal Medicine, Fujita Health University, School of Medicine, Aichi, 470-1192, Japan.
Uchimura
K
K
Makino
M
M
Kobayashi
T
T
Hayashi
R
R
Nagata
M
M
Kakizawa
H
H
Fujiwara
K
K
Nagasaka
A
A
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000097:blood* / Q000276:immunology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006111:Graves Disease / Q000097:blood* / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D017455:Receptors, IgE / Q000235:genetics; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001323:Autoantibodies; D019013:CD40 Antigens; D017455:Receptors, IgE; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D005968:Glutamate Decarboxylase