title: Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence.
abstract: The dramatic decline in immune function with age, especially in T cell proliferative activity, has been documented extensively in experimental animal models and in clinical studies of the elderly. A similar proliferative decline is also seen in long-term T lymphocyte cultures used to study in vitro cellular senescence. We have compared the peripheral blood T lymphocytes of centenarians and younger controls for the cell surface expression of CD28, a costimulatory molecule that is required for optimal activation and proliferation following engagement of the T cell receptor. Our analysis shows a significant decrease (p < 0.001) in the percentage of T cells expressing CD28 in the elderly cohort, with values ranging from 44% to 90%, as compared to the mean control value of 91%. The decline in the percentage of CD28+ T cells correlates with a reduction in the CD4/CD8 ratio (r2 = 0.695, p < 0.0001). Concommitantly, experiments using an in vitro T cell culture system showed a progressive loss of CD28 expression with culture "age." The concordance of proliferative decline and loss of CD28 in the centenarians and in the in vitro cultures suggest that a Hayflick phenomenon may operate in vivo leading to immunosenescence.
authors.affiliation: Department of Pathology and Laboratory Medicine, UCLA School of Medicine 90024, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Effros
authors.forename: N
authors.initials: N
authors.lastname: Boucher
authors.forename: V
authors.initials: V
authors.lastname: Porter
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Spaulding
authors.forename: R L
authors.initials: RL
authors.lastname: Walford
authors.forename: M
authors.initials: M
authors.lastname: Kronenberg
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: F
authors.initials: F
authors.lastname: Schächter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000097:blood*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology; D006801:Humans; D016014:Linear Models; D018655:Lymphocyte Count; D008875:Middle Aged; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens