Age-related differences and common pathways of lymphocyte subsets in sepsis: a comparative review of elderly and pediatric patients

Abstract

Sepsis disproportionately affects older adults and children, two immunologically vulnerable extremes of age. Yet sepsis is superimposed on distinct baselines—immunosenescence in the elderly and immune immaturity in neonates and young children—leading to different pathways toward immune failure. This comparative narrative review synthesizes clinical and experimental evidence on age-specific and shared alterations in lymphocyte subsets in sepsis, including lymphopenia; CD4⁺ and CD8⁺ T cell activation, apoptosis, and exhaustion; B cell depletion and impaired antibody production; NK cell cytotoxic defects; and dynamic regulatory circuits such as Tregs. Recognizing that early organ injury is initiated and amplified primarily by innate immune programs, we frame lymphocyte injury largely as a downstream cost of the acute host-response milieu that can become rate-limiting for immune recovery, secondary infections, and late mortality. We highlight convergent phenotypes linked to secondary infections and late mortality, while emphasizing differences in kinetics, mechanisms, and recovery potential. We propose an age-stratified approach to serial immune monitoring and biomarker-enriched trial design to guide immunoadjuvant therapies and avoid one-size-fits-all immunomodulation. Clarifying these trajectories may improve risk stratification and outcomes across the lifespan.