Immunology

The Long and the Short of It

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Science  04 Jun 2004:
Vol. 304, Issue 5676, pp. 1415
DOI: 10.1126/science.304.5676.1415d

Over a human lifetime, the immune system becomes dominated by an aging lymphocyte population, with the source of new cells diminishing and the existing pool being preserved to fight infection. As with any cell, the normal life span of a lymphocyte is marked by the gradual shortening of its telomeres, eventually resulting in replicative senescence of the cell. However, it is likely that this process is differentially regulated in T lymphocytes, depending on whether they are slowly dividing naïve T cells, short-lived highly proliferating effectors, or long-lived memory cells.

Reed et al. looked at memory cell differentiation in humans who had previously been vaccinated with BCG. After injection of a second antigen, T cells responded vigorously at the site of challenge in the skin, acquiring an activated memory phenotype as they proliferated. Compared with other circulating T cells in these people, the responding cells displayed as much as eight times the level of telomere reduction 3 weeks after vaccination— the amount that would normally be seen in a resting cell over 1 year. Type 1 interferons present at the site of the response were largely responsible for the elevated telomere erosion, apparently through inhibition of the enzyme telomerase, which normally maintains telomere ends. — SJS

J. Exp. Med. 199, 1433 (2004).

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