Publication

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

Journal Paper/Review - Nov 1, 2014

Units
PubMed
Doi
Contact

Citation
Roychoudhuri R, Sékaly R, Restifo N, Cameron M, Gilliet M, Nabel G, Gattinoni L, Goulet J, Hegazy A, Fourati S, Nichols C, Klebanoff C, Ji Y, Pan L, Honda M, Lefebvre F, Flatz L. Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation. Vaccine 2014; 33:914-23.
Type
Journal Paper/Review (English)
Journal
Vaccine 2014; 33
Publication Date
Nov 1, 2014
Issn Electronic
1873-2518
Pages
914-23
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.