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

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

Author information

1
Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: roychoudhuri@mail.nih.gov.
2
Vaccine and Gene Therapy Institute, Port St. Lucie, FL 34987, USA.
3
Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
4
National Cancer Institute (NCI), National Institutes of Bethesda, Bethesda, MD 20892, USA.
5
Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
6
Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
7
Vaccine and Gene Therapy Institute, Port St. Lucie, FL 34987, USA. Electronic address: rpsekaly@vgtifl.org.
8
Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: lukas.flatz@gmail.com.

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.

KEYWORDS:

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

PMID:
25446821
PMCID:
PMC6439469
DOI:
10.1016/j.vaccine.2014.10.007
[Indexed for MEDLINE]
Free PMC Article

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