Hashimoto thyroiditis is characterized by a dense intrathyroidal infiltrate of CD4+ T cells, CD8+ T cells, and CD20+ B cells, with near-universal positivity in patient tissue samples, indicating a robust and sustained local immune response targeting the thyroid gland.

Autoimmune proteins from the thyroid keep triggering immune cells to enter and stay inside the gland. These immune cells include T cells that attack thyroid tissue and B cells that make antibodies. The thyroid cells respond by putting up a molecular brake called PD-L1 to slow down the attack, while special regulatory T cells also stay active to dampen the response. Together, these controls prevent the immune system from destroying the thyroid all at once, so the attack continues slowly for years.