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

Rahul Roychoudhuri, Francois Lefebvre, Mitsuo Honda, Li Pan, Yun Ji, Christopher A. Klebanoff, Carmen N. Nichols, Slim Fourati, Ahmed N. Hegazy, Jean Philippe Goulet, Luca Gattinoni, Gary J. Nabel, Michel Gilliet, Mark Cameron, Nicholas P. Restifo, Rafick P. Sékaly, Lukas Flatz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)914-923
Number of pages10
JournalVaccine
Volume33
Issue number7
DOIs
StatePublished - Feb 11 2015
Externally publishedYes

Keywords

  • Adenovirus vector
  • CD8
  • LCMV vector
  • Memory T cells
  • Prime-boost vaccination
  • T cell memory

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine
  • Medicine(all)

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