A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection
Department of Medicine, Division of Infectious Diseases and Immunology; Program in Molecular Medicine
Genetics | Immunology of Infectious Disease | Medical Immunology | Translational Medical Research
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.
DOI of Published Version
Greenough TC, Straubhaar JR, Kamga L, Weiss ER, Brody RM, McManus MM, Lambrecht LK, Somasundaran M, Luzuriaga KF. A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection. J Immunol. 2015 Nov 1;195(9):4185-97. doi: 10.4049/jimmunol.1401513. Epub 2015 Sep 28. PubMed PMID: 26416268; PubMed Central PMCID: PMC4610856. Link to article on publisher's site
Journal of immunology (Baltimore, Md. : 1950)
Greenough, Thomas C.; Straubhaar, Juerg R.; Kamga, Larisa; Weiss, Eric R.; Brody, Robin M.; McManus, Margaret M.; Lambrecht, Linda K.; Somasundaran, Mohan; and Ruiz De Luzuriaga, Katherine, "A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute EBV Infection" (2015). UMass Center for Clinical and Translational Science Supported Publications. 57.