Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8+CD28(lo) T cells in patients with systemic lupus erythematosus.
To evaluate whether the immune system of systemic lupus erythematosus (SLE) patients shows features of premature aging, we compared telomere length and proliferative potential of SLE peripheral blood mononuclear cells (PBMC) (N = 90) to those of controls (N = 64). SLE samples showed accelerated loss of telomeric DNA (P = 0.00008) and higher levels of senescent (< or =5 kb) telomeric DNA (P = 0.00003). Viability cell counts and CFSE tracking in 6-week-old cell cultures indicated that SLE PBMC (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than controls (P = 0.04). However, a CD8(+)CD28(lo) T cell subset expanded preferentially in SLE-derived bulk cultures (P = 0.0009), preserved telomeric DNA (P = 0.01 vs entire CD8+), and displayed telomerase activity [2.1 telomerase arbitrary units (TAU) vs 0.5 TAU in CD8+CD28(hi) cells and 0.3 TAU in bulk PBMC; P = 0.05]. These T cell anomalies could be due to chronic in vivo stimulation of the immune system and may contribute to the immune dysregulation found in SLE.
Honda
M
M
Department of Medicine, Cedars-Sinai Research Institute and the University of California at Los Angeles, Los Angeles, CA 90048, USA.
Mengesha
E
E
Albano
S
S
Nichols
W S
WS
Wallace
D J
DJ
Metzger
A
A
Klinenberg
J R
JR
Linker-Israeli
M
M
D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
D018106:CD28 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D004247:DNA; D019098:Telomerase; D017493:Leukocyte Common Antigens