Heterogeneity and functional diversity of VZV-specific memory CD4 T cells across age

초록

Aging is a risk factor for increased susceptibility to infectious diseases, including varicella-zoster virus (VZV) reactivation, which manifests as shingles in older individuals. The age-related decline in VZV-specific memory CD4 T cell frequencies correlates with a higher risk of VZV reactivation. However, the heterogeneity and functionality of VZV-specific memory T cells in older individuals remain poorly understood. To address this, we characterized VZV-specific memory CD4 T cells in young and older individuals using single-cell RNA sequencing (scRNA-seq). In older individuals, the CD4 T cell compartment exhibited a shift from naive CD4 T cells toward more differentiated memory and cytotoxic CD4 T cells. Upon activation with cognate antigens, highly proliferative VZV-specific T cells showed considerable heterogeneity, comprising subsets with cycling, less differentiated stem-like, regulatory, and highly differentiated effector features. Notably, individual variability in the effector functions of VZV-specific memory CD4 T cells was prominent and comparable between young and older individuals. This study highlights the complexity and individual heterogeneity of VZV-specific memory T cell responses, providing insights into their diverse functional landscapes across age.