title: Molecular characterization of HCMV-specific immune responses: Parallels between CD8(+) T cells, CD4(+) T cells, and NK cells.
abstract: CD8(+) T cells are important for immunity against human cytomegalovirus (HCMV). The HCMV-specific CD8(+) T-cell response is characterized by the accumulation of terminally differentiated effector cells that have downregulated the costimulatory molecules CD27 and CD28. These HCMV-specific CD8(+) T cells maintain high levels of cytotoxic molecules such as granzyme B and rapidly produce the inflammatory cytokine IFN-γ upon activation. Remarkably, HCMV-specific CD8(+) T cells are able to persist long term as fully functional effector cells, suggesting a unique differentiation pathway that is distinct from the formation of memory CD8(+) T cells after infection with acute viruses. In this review, we aim to highlight the most recent developments in HCMV-specific CD8(+) T-cell differentiation, maintenance, tissue distribution, metabolism and function. HCMV also induces the differentiation of effector CD4(+) T cells and NK cells, which share characteristics with HCMV-specific CD8(+) T cells. We propose that the overlap in differentiation of NK cells, CD4(+) and CD8(+) T cells after HCMV infection may be regulated by a shared transcriptional machinery. A better understanding of the molecular framework of HCMV-specific CD8(+) T-cell responses may benefit vaccine design, as these cells uniquely combine the capacity to rapidly respond to infection with long-term survival.
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Vieira Braga
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Kirsten M L
authors.initials: KM
authors.lastname: Hertoghs
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Klaas P J M
authors.initials: KP
authors.lastname: van Gisbergen
mesh_terms: D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D053804:Granzymes / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D015398:Signal Transduction; D014158:Transcription, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053804:Granzymes
keywords: CD4+ T cell; CD45RA+ CD8+ effector T cell; HCMV; Metabolism; NK cell; Tissue distribution