title: The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines.
abstract: Based on the expression of the TNFR SFP CD27, two Ag-primed CD8(+) T cell subsets can be discerned in the circulation of healthy individuals: CD27(+) T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27(-) T cells, which secrete only IFN-gamma and TNF-alpha. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27(+) to a CD27(-) phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27(-) CD8(+) T cells was found to be linearly related to the total number of CMV-specific CD8(+) T cells. In vitro studies revealed that the acquisition of the CD27(-) phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4(+) T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.
authors.affiliation: Renal Transplant Unit, Department of Internal Medicine, Laboratory for Experimental Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Laila E
authors.initials: LE
authors.lastname: Gamadia
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.forename: Si-La
authors.initials: SL
authors.lastname: Yong
authors.forename: Sugianto
authors.initials: S
authors.lastname: Surachno
authors.forename: Pauline M E
authors.initials: PM
authors.lastname: Wertheim-van Dillen
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: Ten Berge
authors.forename: René A W
authors.initials: RA
authors.lastname: Van Lier
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology*; D053282:CD27 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008024:Ligands; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology; D017735:Virus Latency / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D053282:CD27 Ligand; C505771:CD70 protein, human; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D008565:Membrane Proteins; D010750:Phosphoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa