Immune Deviation Away from Th1 in Interferon-γ Knockout Mice Does Not Enhance TSH Receptor Antibody Production after Naked DNA Vaccination

TSH receptor (TSHR) DNA vaccination induces high TSHR antibody levels in BALB/c mice housed in a conventional facility. However, under pathogen-free conditions, we observed a Th1 cellular response to TSHR antigen characterized by interferon-γ (IFNγ) production. In the present study we investigated t...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2002-04, Vol.143 (4), p.1182-1189
Main Authors: Pichurin, Pavel, Pichurina, Oxana, Chazenbalk, Gregorio D, Paras, Charmaine, Chen, Chun-Rong, Rapoport, Basil, McLachlan, Sandra M
Format: Article
Language:English
Subjects:
Animals
Cytokines - biosynthesis
DNA - immunology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunoglobulin G - immunology
Immunoglobulins, Thyroid-Stimulating
Interferon gamma Receptor
Interferon-gamma - genetics
Interferon-gamma - metabolism
Interferon-gamma - physiology
Mice
Mice, Inbred BALB C
Mice, Knockout
Receptors, Interferon - immunology
Receptors, Thyrotropin - immunology
Receptors, Thyrotropin - isolation & purification
Receptors, Thyrotropin - metabolism
Recombinant Fusion Proteins - immunology
Th1 Cells - metabolism
Thyrotropin - metabolism
Vaccination
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Summary:TSH receptor (TSHR) DNA vaccination induces high TSHR antibody levels in BALB/c mice housed in a conventional facility. However, under pathogen-free conditions, we observed a Th1 cellular response to TSHR antigen characterized by interferon-γ (IFNγ) production. In the present study we investigated the effect on TSHR DNA vaccination of diverting the cytokine milieu away from Th1 using 1) IFNγ knockout BALB/c mice, and 2) wild-type mice covaccinated with DNA for the TSHR and for IFNγ/receptor-Fc protein that prevents IFNγ from binding to its receptor. Neither approach enhanced TSHR antibody levels, although splenocyte IFNγ production in response to TSHR antigen was absent (IFNγ knockouts) or reduced (IFNγ receptor-Fc). Moreover, production of IL-2, another Th1 cytokine, but not Th2 cytokines, indicated that neither strategy overcame the Th1 bias of im DNA vaccination. Importantly, splenocyte production of IFNγ and IL-2 provides a sensitive detection system for TSHR-specific T cells. Unexpectedly, higher TSHR antibody levels developed in rare mice. High titer animals had TSHR-specific responses of both Th2 and Th1 types, whereas low titer animals had Th1-restricted TSHR responses. The heterogeneity of responses induced by TSHR DNA vaccination in mice may provide insight into the titers and IgG subclasses of spontaneous autoantibodies in humans.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.143.4.8745