VACCINE-INDUCED T-CELL MEMORY: SINGLE-CELL RNA-SEQ PROFILING IN POST-VACCINATION LYMPH NODES

Abstract

The development of long-lasting vaccine-induced immunity relies on the generation and maintenance of memory T cells, a process that remains incompletely understood at the single-cell level. In this study, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptional landscape of T cells within lymph nodes at multiple time points following vaccination. Our analysis revealed a dynamic shift from naïve to effector and memory T cell phenotypes, accompanied by significant transcriptional reprogramming. Notably, genes such as IL7R, CD44, and CXCR3 were upregulated in memory T cells, indicating their roles in survival, tissue homing, and immune readiness. Pathway enrichment analysis identified the activation of TCR signaling, cytokine-cytokine receptor interactions, and NF-κB pathways, all of which are critical for effective immune priming and differentiation. Clonotype tracking found strong TCR expansion, while analysis of cytokines proved that IFN-γ, IL-2 and TNF-α were all upregulated, representing optimal effector activity. Moreover, increases in PD-1 and LAG-3 which indicate exhaustion responses, were detected in later stages of the illness, suggesting the start of regulatory feedback. Analysis with ATAC-seq data demonstrated higher accessibility of DNA at critical memory gene locations, suggesting that several genes are controlled together by an organized system of changes to DNA and its activity. All of these results combined make a broad atlas of T cell memory after vaccines. They also identify unique molecular changes that can improve both the current and new vaccines and immunotherapies.