Microsatellite instability in in vitro ageing of T lymphocyte clones.
Repair of mismatches in mammalian cell DNA is mediated by a complex of proteins that constitute the so-called mismatch repair system (MMR), the main post-replicative pathway for the correction of replication errors. Loss of MMR (as exemplified by germline mutations in some MMR genes, leading to hereditary non-polyposis colorectal cancer) results in increased mutation rates at both coding sequences and in non-coding regions such as microsatellites. In order to evaluate possible functional alterations of this repair system during ageing that could affect immune system efficiency, we studied microsatellite instability at five different loci interspersed in the genome (CD4, VWA31, Tpox, Fes/FPS and p53) in total DNA from T lymphocyte clones derived from hematopoietic stem cells, or peripheral T cells of young or elderly subjects. In addition, these clones had been maintained for different periods in vitro to represent a culture model of ageing. We observed increasing instability accumulating with increasing passages in culture, particularly in CD34+cell-derived clones, but no clear donor age relationship.
Neri
Simona
S
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, IOR, Via di Barbiano 1/10, 40136 Bologna, Italy.
Cattini
Luca
L
Facchini
Andrea
A
Pawelec
Graham
G
Mariani
Erminia
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000276:immunology*; D020137:Base Pair Mismatch / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000473:pathology; D004249:DNA Damage / Q000276:immunology; D004260:DNA Repair / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology*