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| Status |
Public on Aug 01, 2013 |
| Title |
CD8+ T-cell memory bears the transcriptional imprint of progressive differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The generation of CD8+ T-cell memory is an important aim of immunization. While several distinct subsets of CD8+ T-cell memory have been described, the lineage relationships between effector (EFF), effector memory (EM) and central memory (CM) T cells remain contentious. Specifically, there is contradictory experimental evidence to support both the linear (Naive>EFF>EM>CM) and progressive differentiation (Naive>CM>EM>EFF) models. In this study, we applied a systems biology approach to examine global transcriptional relationships between the three major CD8+ T cell subsets arising endogenously as a result of vaccination with three different prime-boost vaccine regimens. Differential gene expression analysis and principle component analysis revealed that central memory cells were more closely related to naive T cells than both effector memory and effector cells. When the transcriptional relationships between subsets were enriched in an unbiased fashion with known global transcriptional changes that result when T-cells repeatedly encounter antigen, our analysis favored a model whereby cumulative antigenic stimulation drives differentiation specifically from Naive > CM > EM > EFF. These findings provide an insight into the lineage relationship between mature CD8+ T-cell subsets and will help in the rational design of vaccines aimed at generating effective immune responses against infections and cancer.
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| Overall design |
Effector (EFF), effector memory (EM), central memory (CM) and naive CD8+ T cells from mice spleen. Memory subset arise endogenously as a result of vaccination with three different prime-boost vaccine regimens: DNA-rAd5, rAd5-rAd5 and rAd5-rLCMV.
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| Contributor(s) |
Roychoudhuri R, Lefebvre F, Honda M, Klebanoff CA, Sukumar M, Pan L, Goulet J, Kettaf N, Haddad EK, Gattinoni L, Nabel GJ, Restifo NP, Sékaly RP, Flatz L, Wilkinson PA |
| Citation(s) |
21422297, 25446821 |
| Submission date |
Nov 21, 2012 |
| Last update date |
Feb 07, 2017 |
| Contact name |
Peter A Wilkinson |
| Organization name |
Case Western Reserve University
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| Department |
Pathology / Systems Biology & Bioinformatics
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| Street address |
2103 Cornell Road
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| City |
Cleveland |
| State/province |
Ohio |
| ZIP/Postal code |
44120 |
| Country |
USA |
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| Platforms (1) |
| GPL8389 |
Illumina Mouse-8 Expression BeadChip |
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| Samples (67)
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| Relations |
| BioProject |
PRJNA182004 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42459_non-normalized.txt.gz |
6.2 Mb |
(ftp)(http) |
TXT |
| Raw data are available on Series record |
| Processed data included within Sample table |
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