Long-term in vitro growth of human T cell clones: can postmitotic 'senescent' cell populations be defined?

The long-term in vitro growth characteristics of peripheral, nonspecifically expanded T cell clones from young (< 30 years old) and old (> 65 years old) Senieur-protocol compatible healthy blood donors were compared. Additionally, T cell clones derived from the sites of autoimmune events were studied. Until the 6th week in culture all clones showed a progressive increase in cell number. CD25 expression and proliferation in response to stimulation with recombinant IL-2 remained stable. Staining of DNA fragments with propidium iodide, however, revealed a small percentage of apoptotic cells. After 7-12 weeks in culture a rapid decrease in cell numbers accompanied by a striking increase in the number of apoptotic cells was noted in all peripheral clones. Although CD25 was still present on almost 100% of the cells, receptor density and proliferative response to IL-2 were greatly reduced. After a maximum of 14 weeks in culture, corresponding to 29 population doublings (PD), all peripheral T cell clones had died. No difference was noted between CD4 and CD8 T cell clones, but clones from old donors tended to have a shorter lifespan and a lower number of PD than clones from young persons (n.s.). Interestingly, T cells from autoimmune lesions had a longer lifespan and a higher number of PD than peripheral T cell clones (p < 0.01). In contrast to peripheral T cell clones, which died almost immediately after reaching the end of their proliferative capacity, a small but stable nondividing cell population could be distinguished in autoimmune clones.(ABSTRACT TRUNCATED AT 250 WORDS)