Thyrotrophin receptor-specific memory T cell responses require normal B cells in a murine model of Graves’ disease

Abstract

SUMMARYThe role of B cells as antigen-presenting cells is being recognized increasingly in immune responses to infections and autoimmunity. We compared T cell responses in wild-type and B cell-deficient mice immunized with the thyrotrophin receptor (TSHR), the major autoantigen in Graves' disease. Three B cell-deficient mouse strains were studied: J H D (no B cells), mIgM (membrane-bound monoclonal IgM + B cells) and (m + s)IgM (membrane-bound and secreted monoclonal IgM). Wild-type and B celldeficient mice (BALB/c background) were studied 8 weeks after three injections of TSHR or control adenovirus. Only wild-type mice developed IgG class TSHR antibodies and hyperthyroidism. After challenge with TSHR antigen, splenocyte cultures were tested for cytokine production. Splenocytes from TSHR adenovirus injected wild-type and mIgM-mice, but not from J H D-or (m + s)IgM-mice, produced interferon (IFN)-g in response to TSHR protein. Concanavalin A and pokeweed mitogen induced comparable IFN-g secretion in all groups of mice except in the J H D strain in which responses were reduced. The absence in (m + s)IgM mice and presence in mIgM mice of an anamnestic response to TSHR antigen was unrelated to lymphoid cell types. Surprisingly, although TSHR-specific antibodies were undetectable, low levels of serum IgG were present in mIgM-but not (m + s)IgM mice. Moreover, IFN-g production by antigen-stimulated splenocytes correlated with IgG levels. In conclusion, T cell responses to TSHR antigen developed only in mice with IgG-secreting B cells. Consequently, in the TSHR-adenovirus model of Graves' disease, some normal B cells appear to be required for the development of memory T cells.

ORIGINAL ARTICLE: Gender Dichotomy in Antibody Response in a T‐Cell Lymphoma: Involvement of IL‐13 and Gonadal Hormones

“…We report here for the first time that sex steroids are involved in the differential regulation of IL‐13. It is primarily produced by NKT‐cells and Th2 cells, 25 and both cells are shown to express the receptor for gonadal hormones 26,27 . Therefore, it could be possible that sex steroids are involved in the regulation of IL‐13 production.…”

Immunopathogenesis of Thyroid Eye Disease: Emerging Paradigms

“…This agent blocks CTLA4 association with CD80 and CD86 on antigen-presenting cells, leading to T cell anergy 133. Results with CTLA4 Ig have been promising in an open label phase I trial in rheumatoid arthritis and multiple sclerosis 18,97…”

Lymphocytes in peripheral blood and thyroid tissue in children with Graves’ disease

“…[6] Th2-cells dependent B cells activation leads to over-production of autoantibodies and cytokines. [24,25] It is known, and we observed it too, that patients with untreated GD have an increased number of circulating B cells, which are involved in the production of autoantibodies against thyroid antigens, including CD5+ B cells producing natural autoantibodies. [3,4,26,27] The B cells observed in the thyroid were mainly scattered as single cells or appeared in small groups in the T-lymphocyte infi ltrates characterized by CD20+.…”