Increased Numbers of CD4⁺ 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.