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J Immunol. 2015 Nov 1;195(9):4185-97. doi: 10.4049/jimmunol.1401513. Epub 2015 Sep 28.

A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection.

Author information

1
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; and.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
3
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 Katherine.luzuriaga@umassmed.edu.

Abstract

Virus-specific CD8(+) T cells expand dramatically during acute EBV infection, and their persistence is important for lifelong control of EBV-related disease. To better define the generation and maintenance of these effective CD8(+) T cell responses, we used microarrays to characterize gene expression in total and EBV-specific CD8(+) T cells isolated from the peripheral blood of 10 individuals followed from acute infectious mononucleosis (AIM) into convalescence (CONV). In total CD8(+) T cells, differential expression of genes in AIM and CONV was most pronounced among those encoding proteins important in T cell activation/differentiation, cell division/metabolism, chemokines/cytokines and receptors, signaling and transcription factors (TF), immune effector functions, and negative regulators. Within these categories, we identified 28 genes that correlated with CD8(+) T cell expansion in response to an acute EBV infection. In EBV-specific CD8(+) T cells, we identified 33 genes that were differentially expressed in AIM and CONV. Two important TF, T-bet and eomesodermin, were upregulated and maintained at similar levels in both AIM and CONV; in contrast, protein expression declined from AIM to CONV. Expression of these TF varied among cells with different epitope specificities. Collectively, gene and protein expression patterns suggest that a large proportion, if not a majority of CD8(+) T cells in AIM are virus specific, activated, dividing, and primed to exert effector activities. High expression of T-bet and eomesodermin may help to maintain effector mechanisms in activated cells and to enable proliferation and transition to earlier differentiation states in CONV.

PMID:
26416268
PMCID:
PMC4610856
DOI:
10.4049/jimmunol.1401513
[Indexed for MEDLINE]
Free PMC Article

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