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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 publication

DOI

10.1016/j.vaccine.2014.10.007

Type

Journal article

Journal

Vaccine

Publication Date

11/02/2015

Volume

33

Pages

914 - 923

Keywords

Adenovirus vector, CD8, LCMV vector, Memory T cells, Prime-boost vaccination, T cell memory, Animals, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, Cultured, Female, Flow Cytometry, Immunologic Memory, Mice, Mice, Inbred BALB C, Oligonucleotide Array Sequence Analysis