Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation

Vaccine. 2015 Feb 11;33(7):914-23. doi: 10.1016/j.vaccine.2014.10.007. Epub 2014 Nov 1.


The generation of CD8(+) T-cell memory is a major aim of vaccination. While distinct subsets of CD8(+) T-cells are generated following immunization that differ in their ability to confer long-term immunity against infection, the transcriptional profiles of these subsets within endogenous vaccine-induced CD8(+) T cell responses have not been resolved. Here, we measure global transcriptional profiles of endogenous effector (TEFF), effector memory (TEM) and central memory (TCM) CD8(+) T-cells arising from immunization with three distinct prime-boost vaccine regimens. While a proportion of transcripts were uniquely regulated within distinct CD8(+) T cell populations, we observed progressive up- or down-regulation in the expression of a majority of differentially expressed transcripts when subsets were compared in the order TN>TCM>TEM>TEFF. Strikingly, when we compared global differences in gene expression between TN, TCM, TEM and TEFF cells with known transcriptional changes that result when CD8(+) T cells repetitively encounter antigen, our analysis overwhelmingly favored a model whereby cumulative antigen stimulation drives differentiation specifically from TN>TCM>TEM>TEFF and this was common to all vaccines tested. These findings provide insight into the molecular basis of immunological memory and identify potential biomarkers for characterization of vaccine-induced responses and prediction of vaccine efficacy.

Keywords: Adenovirus vector; CD8; LCMV vector; Memory T cells; Prime-boost vaccination; T cell memory.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Immunologic Memory / immunology
  • Immunologic Memory / physiology
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotide Array Sequence Analysis

Associated data

  • GEO/GSE42459