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


METHODS
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.


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.


CONCLUSIONS
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.
Vogt
Saskia
S
Institut für Immunologie und Medizinische Klinik der Universität Heidelberg, Heidelberg, Germany.
Iking-Konert
Christof
C
Hug
Friederike
F
Andrassy
Konrad
K
Hänsch
G Maria
GM
D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000235:genetics; D016922:Cellular Senescence / Q000502:physiology*; D015870:Gene Expression; D014890:Granulomatosis with Polyangiitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D018106:CD28 Antigens; D019098:Telomerase