Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice

Heng, Tracy S. P., Reiseger, Jessica J., Fletcher, Anne L., Leggatt, Graham R., White, Olivia J., Vlahos, Katerina, Frazer, Ian H., Turner, Stephen J. and Boyd, Richard L. (2012) Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice. PLoS One, 7 8: e42677.1-e42677.11. doi:10.1371/journal.pone.0042677

Author Heng, Tracy S. P.
Reiseger, Jessica J.
Fletcher, Anne L.
Leggatt, Graham R.
White, Olivia J.
Vlahos, Katerina
Frazer, Ian H.
Turner, Stephen J.
Boyd, Richard L.
Title Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1371/journal.pone.0042677
Open Access Status DOI
Volume 7
Issue 8
Start page e42677.1
End page e42677.11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2013
Language eng
Abstract Recent evidence suggests that the decline in resistance to viral infections with age occurs predominantly as a result of a gradual loss of naïve antigen-specific T cells. As such, restoration of the naïve T cell repertoire to levels seen in young healthy adults may improve defence against infection in the aged. We have previously shown that sex steroid ablation (SSA) rejuvenates the ageing thymus and increases thymic export of naïve T cells, but it remains unclear whether T cell responses are improved. Using mouse models of clinically relevant diseases, we now demonstrate that SSA increases the number of naïve T cells able to respond to antigen, thereby enhancing effector responses in aged mice. Specifically, aged mice exhibit a delay in clearing influenza A virus, which correlates with diminished specific cytotoxic activity. This is due to a decreased magnitude of response and not an intrinsic defect in effector T cell function. Upon SSA, aged mice exhibit increased T cell responsiveness that restores efficient viral clearance. We further demonstrate that SSA decreases the incidence of an inducible tumour in aged mice and can potentially increase their responsiveness to a low-dose human papillomavirus vaccine in clearing pre-formed tumours. As thymectomy abrogates the increase in T cell numbers and responsiveness following SSA, we propose that the T cell effects of SSA are dependent on thymic reactivation and subsequent replenishment of the peripheral T cell pool with newly emigrated naïve T cells. These findings have important implications for strategies to improve protection from infection and responsiveness to vaccination in the aged.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e42677

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 24 Oct 2012, 10:54:47 EST by Dr Graham Leggatt on behalf of UQ Diamantina Institute