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

Abstract

The 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: JHD (no B cells), mIgM (membrane-bound monoclonal IgM+ B cells) and (m + s)IgM (membrane-bound and secreted monoclonal IgM). Wild-type and B cell-deficient 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 JHD- or (m + s)IgM- mice, produced interferon (IFN)-gamma in response to TSHR protein. Concanavalin A and pokeweed mitogen induced comparable IFN-gamma secretion in all groups of mice except in the JHD 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-gamma 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.

• Authors: P Pichurin, H Aliesky, C-R Chen, Y Nagayama, B Rapoport, S M McLachlan
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 134 Issue 3 Pg. 396-402 (Dec 2003) ISSN: 0009-9104 [Print] England
• PMID: 14632743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantibodies
• Immunoglobulin G
• Immunoglobulin M
• Receptors, Thyrotropin
• Thyroxine

Topics

• Adenoviridae (genetics)
• Animals
• Autoantibodies (blood)
• B-Lymphocytes (immunology)
• Female
• Genetic Vectors (administration & dosage)
• Graves Disease (immunology)
• Immunoglobulin G (blood)
• Immunoglobulin M (blood)
• Immunologic Memory
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Mutant Strains
• Models, Animal
• Receptors, Thyrotropin (genetics, immunology)
• T-Lymphocytes (immunology)
• Thyroxine (blood)
• Transduction, Genetic (methods)