title: Functional Diversity of Cytomegalovirus-Specific T Cells Is Maintained in Older People and Significantly Associated With Protein Specificity and Response Size.
abstract: BACKGROUND
  Parallel upregulation of several T-cell effector functions (ie, polyfunctionality) is believed to be critical for the protection against viruses but thought to decrease in large T-cell expansions, in particular at older ages. The factors determining T-cell polyfunctionality are incompletely understood. Here we revisit the question of cytomegalovirus (CMV)-specific T-cell polyfunctionality, including a wide range of T-cell target proteins, response sizes, and participant ages.
  
  
  METHODS
  Polychromatic flow cytometry was used to analyze the functional diversity (ie, CD107, CD154, interleukin 2, tumor necrosis factor, and interferon γ expression) of CD4+and CD8+T-cell responses to 19 CMV proteins in a large group of young and older United Kingdom participants. A group of oldest old people (age >85 years) was included to explore these parameters in exceptional survivors. Polyfunctionality was assessed for each protein-specific response subset, by subset and in aggregate, across all proteins by using the novel polyfunctionality index.
  
  
  RESULTS
  Polyfunctionality was not reduced in healthy older people as compared to young people. However, it was significantly related to target protein specificity. For each protein, it increased with response size. In the oldest old group, overall T-cell polyfunctionality was significantly lower.
  
  
  CONCLUSIONS
  Our results give a new perspective on T-cell polyfunctionality and raise the question of whether maintaining polyfunctionality of CMV-specific T cells at older ages is necessarily beneficial.
authors: Division of Medicine.
authors: Martha
authors: M
authors: Bajwa
authors: Institute Pasteur, Cenci-Bolognetti Foundation, Department of Public Health and Infectious Diseases, University Sapienza of Rome.
authors: Serena
authors: S
authors: Vita
authors: Dipartimento di Medicina Interna e Scienze Biomediche, Università di Parma, Italy.
authors: Rosanna
authors: R
authors: Vescovini
authors: Inserm UMR-S1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris).|AP-HP, Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
authors: Martin
authors: M
authors: Larsen
authors: Dipartimento di Medicina Interna e Scienze Biomediche, Università di Parma, Italy.
authors: Paolo
authors: P
authors: Sansoni
authors: School of Pharmacy and Biomolecular Sciences, University of Brighton, United Kingdom.
authors: Nadia
authors: N
authors: Terrazzini
authors: Division of Medicine.
authors: Stefano
authors: S
authors: Caserta
authors: Division of Medicine.
authors: David
authors: D
authors: Thomas
authors: Division of Medicine.
authors: Kevin A
authors: KA
authors: Davies
authors: Division of Primary Care and Public Health Brighton and Sussex Medical School, United Kingdom.
authors: Helen
authors: H
authors: Smith
authors: Division of Medicine.
authors: Florian
authors: F
authors: Kern
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D006113:United Kingdom; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: CD4+ T cells; CMV target proteins; T-cell polyfunctionality; cytomegalovirus