Shortening of telomeres: Evidence for replicative senescence of T cells derived from patients with Wegener's granulomatosis.

Abstract

Replicative senescence describes the fact that somatic cells undergo a finite and predictable number of cell divisions before entering an irreversible state of growth arrest. Progressive shortening of the telomeres, a consequence of cell division, is a reliable indicator of replicative senescence. We analyzed telomere length of DNA derived from T cells of patients suffering from Wegener's granulomatosis by Southern blotting. Moreover, expression of CD28, another marker for replicative senescence, was tested by cytofluorometry. In patients with disease for more than 5 years, short telomeres were detected in addition to telomeres of normal length, indicating replicative senescence of discrete T-cell clones. Reduced expression of CD28 was noted, particularly on CD8-positive T cells, derived from patients with disease for more than 5 years and short telomeres. Our data provide evidence that a portion of T cells had undergone replicative senescence, which in turn indicates clonal expansion of T cells as consequence of activation.