title: A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection.
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.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; and.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Greenough
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Juerg R
authors.initials: JR
authors.lastname: Straubhaar
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Larisa
authors.initials: L
authors.lastname: Kamga
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Weiss
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Brody
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: McManus
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Linda K
authors.initials: LK
authors.lastname: Lambrecht
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Mohan
authors.initials: M
authors.lastname: Somasundaran
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 Katherine.luzuriaga@umassmed.edu.
authors.forename: Katherine F
authors.initials: KF
authors.lastname: Luzuriaga
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology*; D008297:Male; D020395:Receptors, Interleukin-7 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D020395:Receptors, Interleukin-7; D014157:Transcription Factors; D051997:ADP-ribosyl Cyclase 1