title: CMV-Specific T-cell Responses at Older Ages: Broad Responses With a Large Central Memory Component May Be Key to Long-term Survival.
abstract: Cytomegalovirus (CMV) infection sometimes causes large expansions of CMV-specific T cells, particularly in older people. This is believed to undermine immunity to other pathogens and to accelerate immunosenescence. While multiple different CMV proteins are recognized, most publications on age-related T-cell expansions have focused on dominant target proteins UL83 or UL123, and the T-cell activation marker interferon-γ (IFN-γ). We were concerned that this narrow approach might have skewed our understanding of CMV-specific immunity at older ages. We have, therefore, widened the scope of analysis to include in vitro-induced T-cell responses to 19 frequently recognized CMV proteins in "young" and "older" healthy volunteers and a group of "oldest old" long-term survivors (>85 years of age). Polychromatic flow cytometry was used to analyze T-cell activation markers (CD107, CD154, interleukin-2 [IL-2], tumor necrosis factor [TNF], and IFN-γ) and memory phenotypes (CD27, CD45RA). The older group had, on average, larger T-cell responses than the young, but, interestingly, response size differences were relatively smaller when all activation markers were considered rather than IFN-γ or TNF alone. The oldest old group recognized more proteins on average than the other groups, and had even bigger T-cell responses than the older group with a significantly larger central memory CD4 T-cell component.
authors.affiliation: Department of Clinical and Experimental Medicine.
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, and.
authors.forename: Serena
authors.initials: S
authors.lastname: Vita
authors.affiliation: Dipartimento di Clinica Sperimentale, Università di Parma, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Vescovini
authors.affiliation: Inserm UMR-S1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), and.|AP-HP, Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, Paris, France ; and.
authors.forename: Martin
authors.initials: M
authors.lastname: Larsen
authors.affiliation: Dipartimento di Clinica Sperimentale, Università di Parma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sansoni
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, United Kingdom.
authors.forename: Nadia
authors.initials: N
authors.lastname: Terrazzini
authors.affiliation: Department of Global Health and Infection, and.
authors.forename: Stefano
authors.initials: S
authors.lastname: Caserta
authors.affiliation: Department of Clinical and Experimental Medicine.
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Department of Clinical and Experimental Medicine.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Davies
authors.affiliation: Department of Primary Care and Public Health and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Smith
authors.affiliation: Department of Clinical and Experimental Medicine.
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Ageing; Central memory T-cells; Cytomegalovirus; Response breadth.; T-cell memory inflation; T-cells