title: Differentiation of cytomegalovirus-specific CD8(+) T cells in healthy and immunosuppressed virus carriers.
abstract: During immunosuppression, cytomegalovirus (CMV) can reactivate and cause serious clinical problems. Normally, abundant virus replication is suppressed by immune effector mechanisms. To study the interaction between CD8(+) T cells and persisting viruses, frequencies and phenotypes of CMV-specific CD8(+) T cells were determined in healthy individuals and compared to those in renal transplant recipients. In healthy donors, function of circulating virus-specific CD8(+) T cells, as measured by peptide-induced interferon gamma (IFN-gamma) production, but not the number of virus-specific T cells enumerated by binding of specific tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN-gamma-secreting CD4(+) helper T cells. Circulating CMV- specific CD8(+) T cells did not express CCR7 and may therefore not be able to recirculate through peripheral lymph nodes. Based on coexpression of CD27 and CD45R0 most CMV-specific T cells in healthy donors appeared to be memory-type cells. Remarkably, frequencies of CMV-specific CD8(+) T cells were significantly higher in immunosuppressed individuals than in healthy donors. In these patients CMV-specific cells predominantly had an effector phenotype, that is, CD45R0(+)CD27(-)CCR7(-) or CD45RA(+)CD27(-)CCR7(-) and contained both granzyme B and perforin. Our data show that in response to immunosuppressive medication quantitative and qualitative changes occur in the CD8(+) T-cell compartment. These adaptations may be instrumental to maintain CMV latency. (Blood. 2001;98:754-761)
authors.affiliation: Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, The Netherlands Cancer Institute, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. l.e.gamadia@amc.uva.nl
authors.forename: L E
authors.initials: LE
authors.lastname: Gamadia
authors.forename: R J
authors.initials: RJ
authors.lastname: Rentenaar
authors.forename: P A
authors.initials: PA
authors.lastname: Baars
authors.forename: E B
authors.initials: EB
authors.lastname: Remmerswaal
authors.forename: S
authors.initials: S
authors.lastname: Surachno
authors.forename: J F
authors.initials: JF
authors.lastname: Weel
authors.forename: M
authors.initials: M
authors.lastname: Toebes
authors.forename: T N
authors.initials: TN
authors.lastname: Schumacher
authors.forename: I J
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: R A
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology*; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology; D053804:Granzymes; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D016130:Immunophenotyping; D016030:Kidney Transplantation / Q000276:immunology; D008137:Longitudinal Studies; D011971:Receptors, Immunologic / Q000378:metabolism; D054340:Receptors, KIR; D012697:Serine Endopeptidases / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014775:Virus Activation
chemical_list: D006680:HLA Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases