Noncanonical cytotoxicity: lipid scavenging by metabolically dysregulated colonic CD8+ T cells induces epithelial damage in people with HIV.

Metabolically disrupted CD8+ T cells drive epithelial injury in people with HIV (PWH) receiving antiretroviral therapy (ART). In colonic tissue-resident memory (TRM) CD8+ T cells, impaired peroxisome proliferator-activated receptor γ (PPARγ)-dependent lipid metabolism triggers aberrant lipid scavenging from epithelial cell membranes through direct cell contact, leading to epithelial apoptosis and barrier disruption.