Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice

Area of Science:

• Immunology
• Endocrinology
• Autoimmunity

Background:

• NOD.H-2h4 mice spontaneously develop autoimmune thyroiditis (SAT) and anti-thyroglobulin autoantibodies.
• SAT incidence reaches nearly 100% in both sexes after 6-8 weeks of 0.05% NaI in drinking water.
• Thyroid inflammation becomes chronic over 3-4 months after reaching maximum severity.

Purpose of the Study:

• To investigate the role of T cells and cytokines in the development and maintenance of autoimmune thyroiditis in NOD.H-2h4 mice.
• To analyze the cytokine profiles associated with different phases of SAT.
• To determine the involvement of CD4+ and CD8+ T cells in SAT pathogenesis.

Main Methods:

• Administration of 0.05% NaI in drinking water to NOD.H-2h4 mice.
• Monitoring of SAT incidence, severity, and autoantibody production.
• T cell depletion studies (CD4+ and CD8+).
• Analysis of cytokine gene expression in thyroid tissues.

Main Results:

• NOD.H-2h4 mice developed SAT and anti-mouse thyroglobulin (MTg) IgG1 and IgG2b autoantibodies after NaI administration.
• Both CD4+ and CD8+ T cells were involved in initial SAT development.
• Depletion of CD4+ T cells, but not CD8+ T cells, reduced SAT severity, indicating their requirement for both development and maintenance.
• Both Th1 and Th2 cytokines were expressed, with Th1 cytokines peaking early and Th2 cytokines later during the chronic phase.
• Transforming growth factor-beta (TGF-β) was highly expressed in NOD.H-2h4 thyroids regardless of NaI exposure or lesion presence.

Conclusions:

• CD4+ T cells are essential for the development and maintenance of autoimmune thyroiditis in NOD.H-2h4 mice.
• SAT pathogenesis involves a dynamic interplay of Th1 and Th2 immune responses.
• TGF-β may play a significant role in the thyroid microenvironment of these mice, independent of active disease induction by NaI.