Increased Numbers of <scp>CD4</scp> ⁺ T‐Cells in the Hypocretin/Orexin Region of Narcolepsy Type 1

Narcolepsy type 1 (NT1) is presumed to be an autoimmune disorder caused by hypothalamic loss of hypocretin (Hcrt; orexin). In postmortem NT1 brains, we observed an 11‐fold increase of CD4 + T‐cells in the Hcrt region compared with control hypothalami, without a corresponding rise in CD8 + T‐cells. CD4 + and CD8 + T‐cell numbers were unchanged in other hypothalamic regions, including the paraventricular nucleus and median eminence, and in extra‐hypothalamic areas such as the substantia nigra and locus coeruleus. Hcrt‐region CD4 + T‐cells expressed the tissue‐resident memory markers CD49a and CXCR6. These findings support the autoimmune hypothesis of NT1. ANN NEUROL 2026;99:1173–1178