DNA damage recognition and repair capacities in human naïve and memory T cells from peripheral blood of young and elderly subjects.
T cells accumulate genetic damage over time but nai;ve cells display higher genomic stability and longer lifespan as compared to memory cells. We found in nai;ve and memory T cells from young and elderly subjects that DNA damage in unirradiated cells is higher in memory than in nai;ve T cells, and is increased by radiation in both cell types. Repair of the radiation-induced DNA damage was much higher in nai;ve than in memory T cells from young subjects but null in both cell types from elderly subjects. Molecular mechanisms involved in DNA damage recognition and repair were analyzed in both cell subsets from young subjects. The intracellular distribution and amount of the DNA-dependent protein kinase (DNA-PK) complex components (ku 70, ku 80, DNA-PKcs), which are involved in the recognition and repair of DNA breaks caused by ionizing radiations, V(D)J recombination and isotype switching, was assessed in nai;ve and memory T cells from young subjects. While the expression of ku 70 and ku 80 was at comparable levels in both T cell subsets, DNA-PKcs, phosphorylated ku 80, and DNA-binding of ku 70/80 were mostly evident in nai;ve but negligible or absent in memory T cells. These findings may account for the higher genomic stability and longer lifespan of nai;ve as compared to memory human T cells from young subjects.
Scarpaci
Salvatore
S
Department of Biology, University of Rome Tor Vergata, Laboratory of Immunology, Via della Ricerca Scientifica, 00133, Rome, Italy.
Frasca
Daniela
D
Barattini
Paola
P
Guidi
Luisa
L
Doria
Gino
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000276:immunology*; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage / Q000276:immunology*; D004265:DNA Helicases; D004260:DNA Repair / Q000276:immunology*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D000072200:Ku Autoantigen; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D017493:Leukocyte Common Antigens; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen