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.
Rights and Permissions
Citation: 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
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.