Journal
CLINICAL IMMUNOLOGY
Volume 99, Issue 2, Pages 211-221Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/clim.2001.5023
Keywords
SLE; T lymphocyte aging; telomere length; autoimmunity
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Funding
- NIAMS NIH HHS [AR4029] Funding Source: Medline
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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 (less than or equal to5 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. (C) 2001 Academic Press.
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