Publication
Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation
Journal Paper/Review - Nov 1, 2014
Roychoudhuri Rahul, Sékaly Rafick P, Restifo Nicholas P, Cameron Mark, Gilliet Michel, Nabel Gary J, Gattinoni Luca, Goulet Jean-Philippe, Hegazy Ahmed N, Fourati Slim, Nichols Carmen N, Klebanoff Christopher A, Ji Yun, Pan Li, Honda Mitsuo, Lefebvre Francois, Flatz Lukas
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PubMed
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Issn Electronic
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Brief description/objective
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.