Metabolic Adaptations Rewire CD4 T Cells in a Subset-Specific Manner in Human Critical Illness with and without Sepsis

Bioenergetic dysfunction is an archetypal finding in critical illness, particularly among patients with severe sepsis. A central feature of sepsis is the shift towards pathologic immunosuppression, especially among CD4 T cells, predisposing to secondary infections and ineffectual organ recovery. However, it remains unknown whether metabolic abnormalities contribute to CD4 T cell dysregulation in critically ill sepsis patients. We collected PBMC from medical and surgical ICU patients at Vanderbilt University Medical Center or community-matched healthy controls. We performed single cell RNA-sequencing with 10x Genomics droplet-based technology on a subset of 9 healthy controls, 19 ICU patients without sepsis, and 19 ICU patients with sepsis to generate a 644,147 cell map of critical illness.