title: Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life.
abstract: During aging, the thymus undergoes a marked involution that is responsible for profound changes in the T-cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T-cell receptor rearrangement excision circles (TREC). A new method based upon real-time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six-color cytofluorimetric analysis revealed that centenarians had an extremely low number of naïve T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20-45) or middle-aged (aged 58-62) donors. Interleukin (IL)-7 and IL-7 receptor alpha-chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real-time PCR. However, IL-7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naïve T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long-living lymphocytes that have not yet encountered their antigen. IL-7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.
authors.affiliation: Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia School of Medicine, via Campi 287, 41100 Modena, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Leonarda
authors.initials: L
authors.lastname: Troiano
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraresi
authors.forename: Elena
authors.initials: E
authors.lastname: Monterastelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Mussi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Salvioli
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging; D016022:Case-Control Studies; D002454:Cell Differentiation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D015851:Interleukin-7 / Q000378:metabolism*; D008136:Longevity / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
chemical_list: D015851:Interleukin-7; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7