Editors' ChoiceImmunology

My Thymus: Still Here When I Need You the Most

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Science Translational Medicine  31 Oct 2012:
Vol. 4, Issue 158, pp. 158ec194
DOI: 10.1126/scitranslmed.3005201

When times are tough, you count on tapping into your reserves to carry you through. But, during acute infection, the thymus—the reservoir for new T cells—actually involutes. Ross et al. investigate the infection-induced contraction of this organ, which is responsible for replenishing the peripheral T cell pool. Their results from mice with targeted genetic deficiencies challenge our current understanding of the mechanism for thymic atrophy and show that the shrunken organ actually still keeps its promise to make new T cells, even during the hard times of infection.

Ross et al. tested (and refute) two leading hypotheses to explain thymic contraction. The first was that infection-induced T cell expansion negatively regulates thymic mass. By showing that thymic involution occurs even in mice without peripheral T cells, they eliminated this explanation. Because high doses of steroids can, independently, precipitate thymic involution, endogenous steroids also have been posited to cause thymic cell loss. The authors showed that mice with targeted disruption of steroid metabolism still developed infection-induced thymic involution. Their conclusion: Endogenous stress-steroids are an unlikely cause of thymic involution during infection.

Next, by meticulously calculating cell numbers during thymic contraction, Ross et al. found that most thymic T-cell precursor populations did contract, but two key cell types were largely maintained. The cells that enter the thymus to become T cells—early thymic precursors—and the all-important cells that leave the thymus to join the peripheral T cell pool—recent thymic emigrants—were comparatively preserved after infection.

So, to its credit, the thymus doesn’t give up when the going gets tough. By careful analysis in a relevant clinical model, Ross et al. revealed that the most critical function of the thymus (T cell generation) is preserved, despite involution, and ruled out two likely causes of involution. This thorough study shows that our friend the thymus remains active, even during hard times.

E. A. Ross et al., Thymic function is maintained during Salmonella-induced atrophy and recovery, J. Immunol. 189, 4266–4274 (2012). [Online Journal]

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