title: NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system.
abstract: Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset. Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3% (interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10(-10)). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the NKG2D+ cells belonged to the CD28(null) compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion, CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system.
authors.affiliation: Histocompatibility Unit, Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Alonso-Arias
authors.forename: Marco A
authors.initials: MA
authors.lastname: Moro-García
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Vázquez
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: José
authors.initials: J
authors.lastname: Baltar
authors.forename: Francisco M Suárez
authors.initials: FM
authors.lastname: García
authors.forename: Juan J Solano
authors.initials: JJ
authors.lastname: Jaurrieta
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007252:Influenza Vaccines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D016176:T-Lymphocyte Subsets; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D007252:Influenza Vaccines; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K