Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10963425 | Vaccine | 2015 | 10 Pages |
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 TNÂ >Â TCMÂ >Â TEMÂ >Â 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 TNÂ >Â TCMÂ >Â TEMÂ >Â 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.
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Authors
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,