Impact of cytomegalovirus-infection on ageing of the immune system

Sara van den Berg

Promoter:
Prof.dr D. (Debbie) van Baarle
Co-promoter:
Dr J.A.M. (José) Borghans & dr J. (Jelle) de Wit
Date:
November 18, 2020
Time:
14:30 h

Summary

Ageing of the immune system leads to impaired immune responses in older individuals. Latent infection with cytomegalovirus (CMV) is thought to accelerate  ageing of the immune system. CMV is a common herpes virus that infects the majority of the worldwide population. CMV remains in individuals for life as a latent infection, though it usually stays asymptomatic. The effort to control CMV is expected to take its toll, and CMV is therefore thought to reduce the functioning of the immune system over time.

This thesis examines the impact of CMV infection on ageing of the immune system. The first part assesses the impact of CMV on the influenza virus-specific immune response, a relevant age-impaired immune function. We show that CMV does not negatively affect the influenza immune response, both to vaccination and infection. The second part of this thesis focuses on the impact of CMV on the T-cell pool. CMV and age establish comparable changes in the T-cell pool. We show that CMV-specific T-cells, present in unusually high numbers, seem unique in their phenotype. However, maintenance of CMV-specific T-cell numbers requires no altered T-cell dynamics. In addition, we show that CMV-specific T-cell numbers are not accumulating over time, and instead develop shortly after primary CMV infection. Higher age at primary infection may lead to higher CMV-specific T-cell numbers.

This research suggests that CMV has a smaller role in the decline of the functioning of the immune system than was previously anticipated, and contributes to our understanding of the unique CMV-specific immune response.