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 an d 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 o r 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 C D4(+) T cells) underwent fewer mitotic cycles and had shorter telomeres tha n controls (P = 0.04). However, a CD8(+)CD28(lo) T cell subset expanded pre ferentially in SLE-derived bulk cultures (P = 0.0009), preserved telomeric DNA (P = 0.01 vs entire CD8(+)), and displayed telomerase activity [2.1 tel omerase arbitrary units (TAU) vs 0.5 TAU in CD8(+)CD28(hi) cells and 0.3 TA U in bulk PBMC; P = 0.05]. These T cell anomalies could be due to chronic i n vivo stimulation of the immune system and may contribute to the immune dy sregulation found in SLE. (C) 2001 Academic Press.