Measurement of lymphocyte lifespan

Most methods of measuring lifespan rely on identifying cells that have gone through cell cycle and, therefore, the usual definition of lifespan is the period elapsing between cell divisions (intermitotic lifespan). This is usually assessed by labeling cells in cycle with identifiable DNA precursors such as tri-tiated thymidine (['HJTdR) or bromodeoxyuridine (BrdU). Obviously, some cells (e.g. plasma cells) may not divide once derived from a precursor population and leave the system through cell death. However, all cells of the immune system are derived from cycling precursors in primary lymphoid organs, and so the rate of accumulation of labeled cells during continu ous infusion of [ 'HJTdR can be used as a measure of the 'average lifespan' within a population. This method has its drawbacks: if too much label is used it can have direct toxic effects on lymphocytes, or indirectly cause polyclonal activation due to breakdown of the intestinal wall. If too little label is used, rapid decay of the DNA precursors in vivo leads to an underestimate of cycling cells. Other methods are available, such as the selective killing of cycling cells by cytotoxic drugs (e.g. hydroxyurea). Persistence of marked cells after adoptive transfer only gives an estimate of the clonal lifespan, as it does not take into account cell division subsequent to transfer.

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