Self-reactive CD4+ T cells and B cells in the blood in health and autoimmune disease: increased frequency of thyroglobulin-reactive cells in Graves' disease.
The mechanisms underlying activation of potentially self-reactive circulating B cells and T cells remain unclear. We measured the uptake of a self-antigen, thyroglobulin, by antigen presenting cells, and the subsequent proliferation of CD4(+) T cells and B cells from healthy controls and patients with autoimmune thyroiditis. In Hashimoto's thyroiditis, B cells bound increased amounts of thyroglobulin in a complement- and autoantibody-dependent manner, and the thyroglobulin-elicited proliferation of CD4(+) T cells and B cells was complement dependent. Increased proportions of Tg-responsive CD4(+) T cells and B cells were found in patients with Graves' disease. Notably, both patient groups and healthy controls exhibited higher proliferative responses to thyroglobulin than to a foreign recall antigen, tetanus toxoid. Our results suggest that self-tolerance can be broken by exposure of circulating lymphocytes to high local concentrations of self-antigen, and that complement plays a role in the maintenance of autoimmune processes, at least in Hashimoto's thyroiditis.
Nielsen
Claus H
CH
Institute for Inflammation Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Moeller
Ane Christine
AC
Hegedüs
Laszlo
L
Bendtzen
Klaus
K
Leslie
R Graham Q
RG
D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D013954:Thyroglobulin / Q000097:blood / Q000276:immunology / Q000494:pharmacology*
D001323:Autoantibodies; D003165:Complement System Proteins; D013954:Thyroglobulin