title: Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts.
abstract: Long term in vitro culture of clonally expanded CD8+T cells, generally found within the CD57+ or CD28-subset, has generally been unsuccessful, suggesting that these cells may have a limited replicative potential. Telomeric shortening may reflect the action of a "mitotic clock" regulating the number of divisions a cell can undergo. In this study, we have compared the telomeric lengths of CD28-CD8+ and CD28+CD8+ T cells in 10 normal individuals to assess their replicative history. Overall, the telomeric lengths were found to be significantly shorter in the CD28-CD8+ T cell subset compared with the CD28+CD8+ subset. Furthermore, clonally expanded TCRBV11+CD8+ T cells from an individual exhibited telomeric lengths that were 2.9 kb shorter than those found in the polyclonal CD28+CD8+ T cell subset. These findings indicate that clonally expanded CD28-CD8+ T cells have undergone many more rounds of replication than CD28+CD8+ T cells, and consistent with the loss of CD28 expression, they may have reached a state of replicative senescence.
authors.affiliation: Department of Medicine, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030, USA.
authors.forename: J
authors.initials: J
authors.lastname: Monteiro
authors.forename: F
authors.initials: F
authors.lastname: Batliwalla
authors.forename: H
authors.initials: H
authors.lastname: Ostrer
authors.forename: P K
authors.initials: PK
authors.lastname: Gregersen
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D006801:Humans; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics; D016615:Telomere / Q000737:chemistry / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta