Autoimmune hypophysitis is classified as primary if its origin is idiopathic and secondary if it develops as a consequence of treatment with
immune checkpoint inhibitors. Expanding use of
immunotherapy has been paralleled by the increasing
hypophysitis prevalence. However, understanding of the immune responses driving the disease remains limited. Using a mouse model of primary
hypophysitis, we have identified CD4+ T lymphocytes to be the main pituitary-infiltrating immune cell population. Functional analysis showed that they display a Th17 and Th1/Th17 phenotype. To examine involvement of proinflammatory Th1, Th17, and Th1/17 subsets in
hypophysitis, we have isolated
RNA from the
formalin-fixed
paraffin-embedded pituitary specimens from 16
hypophysitis patients (three of whom had
hypophysitis secondary to
immune checkpoint inhibitors), 10 patients with
adenoma, and 23 normal pituitaries obtained at autopsy. Transcript levels of IFN-γ,
IL-17A,
IL-4,
IL-10, TGF-β, CD4, CD8α, and class II MHC
transactivator were analyzed by the reverse transcription-quantitative PCR (RT-qPCR). Pituitary glands of patients with
hypophysitis showed significantly higher
IL-17A, CD4, and class II MHC
transactivator mRNA levels compared with
adenoma and normal pituitaries. All three secondary
hypophysitis patients showed detectable
IL-17A levels, but other
cytokines were not detected in their pituitaries. Levels of IFN-γ,
IL-4,
IL-10, and TGF-β did not differ between the groups. TGF-β transcript was found in significantly fewer
hypophysitis pituitaries (2 out of 16) compared with
adenoma (7 out of 10) and normal pituitaries (11 out of 23). Presence of TGF-β in two
hypophysitis patients was associated with significantly lower
IL-17A mRNA levels compared with
hypophysitis patients with no detectable TGF-β (p = 0.03).