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

Abstract

Background. 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. Method. We analyzed telomere length of DNA derived from T cells of patients suffering from Wegener's granulomatosis by Sourthern blotting, Moreover, expression of CD28, another marker for replicative senescence, was tested by cytofluorometry. Results. 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. Conclusion, 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.