title: Cytomegalovirus infection modulates the phenotype and functional profile of the T-cell immune response to mycobacterial antigens in older life.
abstract: Infection with Cytomegalovirus is associated with accelerated immunosenescence. Expansions of CMV-specific T cell responses have previously been demonstrated to affect the ability of T cells to respond to other infections. Most people above 60years of age display M. tuberculosis-specific immunity because of vaccination, exposure, or both. T-cell responses can be assessed by measuring intracellular IFN-γ in vitro after tuberculin stimulation. Here we investigated tuberculin-specific CD4 T-cell responses in independently living healthy older people in the South of England using flow-cytometry. Individuals were investigated for tuberculin and CMV-specific T-cell immunity using in vitro antigen stimulation followed by intracellular staining for IFN-γ, TNF-α, IL2, as well as degranulation and CD154 upregulation. We also examined a control group of younger individuals (20-35years of age). There was no significant difference between older and young people in regards to tuberculin responsiveness of CD4 T-cells; however, older people seemed to show more outliers. Increased responsiveness to tuberculin was significantly correlated to CMV responsiveness but not age. In older donors, the memory phenotype of tuberculin-induced T-cells was significantly skewed towards a more terminal differentiation phenotype in CMV-infected compared to uninfected individuals and the degree of skewing correlated quantitatively with the size of the CMV-specific CD4 T-cell response. This is a fundamental advance over previous reports of changes of the tuberculin-specific CD4 T-cell response with CMV serostatus. Our results show that how the immune system responds to CMV has a fundamental impact on the phenotype and function of the immune response to mycobacterial antigens in older life.
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom; School of Health, Sport and Bioscience, University of East London, London, United Kingdom.
authors.forename: Nadia
authors.initials: N
authors.lastname: Terrazzini
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Martha
authors.initials: M
authors.lastname: Bajwa
authors.affiliation: Institute Pasteur, Cenci-Bolognetti Foundation, Department of Public Health and Infectious Diseases, University Sapienza of Rome, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Vita
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Division of Primary Care and Public Health, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Smith
authors.affiliation: Dipartimento di Medicina Interna e Scienze Biomediche, Università di Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Vescovini
authors.affiliation: Dipartimento di Medicina Interna e Scienze Biomediche, Università di Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sansoni
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom. Electronic address: f.kern@bsms.ac.uk.
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
mesh_terms: D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007202:Indicators and Reagents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010641:Phenotype; D014373:Tuberculin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000942:Antigens, Bacterial; D007202:Indicators and Reagents; D007376:Interleukin-2; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Cytomegalovirus; Flow-cytometry; Immunosenescence; T-cell response; Tuberculosis