title: Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons.
abstract: In spite of the present belief that latent cytomegalovirus (CMV) infection drives CD8+ T-cell differentiation and induces premature immune senescence, no systematic studies have so far been performed to compare phenotypical and functional changes in the CD8+ T-cell repertoire in CMV-infected and noninfected persons of different age groups. In the present study, number, cytokine production, and growth potential of naive (CD45RA+ CD28+), memory (CD45RA- CD28+), and effector (CD45RA+ CD28- or CD45RA- CD28-) CD8+ T cells were analyzed in young, middle-aged, and elderly clinically healthy persons with a positive or negative CMV antibody serology. Numbers and functional properties of CMVpp65(495-503)-specific CD8+ T cells were also studied. We demonstrate that aging as well as CMV infection lead to a decrease in the size of the naive CD8+ T-cell pool but to an increase in the number of CD8+ effector T cells, which produce gamma interferon but lack substantial growth potential. The size of the CD8+ memory T-cell population, which grows well and produces interleukin-2 (IL-2) and IL-4, also increases with aging, but this increase is missing in CMV carriers. Life-long latent CMV infection seems thus to diminish the size of the naive and the early memory T-cell pool and to drive a Th1 polarization within the immune system. This can lead to a reduced diversity of CD8 responses and to chronic inflammatory processes which may be the basis of severe health problems in elderly persons.
authors.affiliation: Immunology Division, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg, 10, A-6020 Innsbruck, Austria.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Susanne
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jenewein
authors.forename: Michael
authors.initials: M
authors.lastname: Keller
authors.forename: Dietmar
authors.initials: D
authors.lastname: Herndler-Brandstetter
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
authors.forename: Diether
authors.initials: D
authors.lastname: Schönitzer
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
chemical_list: D000914:Antibodies, Viral; D018106:CD28 Antigens; D016207:Cytokines; D017493:Leukocyte Common Antigens
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