CD4+ T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice.

摘要: Immune-related adverse events induced by anti–programmed cell death–1 antibodies (PD-1-Ab), including destructive thyroiditis (thyroid-irAE), are thought to be caused activated T cells. However, the subsets that directly responsible for damaging self-organs remain unclear. To clarify which involved in development of thyroid-irAE, a mouse model thyroid-irAE was analyzed. PD-1-Ab administration 2.5 months after immunization with thyroglobulin thyroiditis. Thyroiditis completely prevented previous depletion CD4+ cells and partially depleting CD8+ The frequencies central effector memory secretion interferon-γ stimulation were increased cervical lymph nodes mice compared controls. Histopathological analysis revealed infiltration expressing granzyme B thyroid glands major histocompatibility complex class II expression on thyrocytes thyroid-irAE. Adoptive transfer from destruction follicular architecture irradiated recipient mice. Flow cytometric analyses showed cytotoxic marker CD27 higher peripheral blood mononuclear collected patients versus those without. These data suggest critical role pathogenesis