The Role of CMV in Immunosenescence

Ludmila MQiler, Klaus Hamprecht, and Graham Pawelec


The term “immunosenescence” is commonly taken to mean age-associated changes in immune parameters hypothesized to contribute to increased susceptibility and severity of the older adult to infectious disease, autoimmunity and cancer. In humans, it is characterized by lower numbers and frequencies of naive T and B cells and higher numbers and frequencies of late-differentiated T cells, especially CD8+ T cells, in the peripheral blood. The latter may be very noticeable, but intriguingly, only in people infected by human herpesvirus 5 (Cytomegalovirus, CMV). Almost all human studies have been cross-sectional, thus documenting differences between old and young populations, but not necessarily changes over time. Nonetheless, limited longitudinal studies have provided data consistent with gradually decreasing naive T and B cells, and increasing late-differentiated T cells over time, and in rare instances associating these changes with increasing frailty and incipient mortality in the elderly. Low numbers of naive cells render the aged highly susceptible to pathogens to which they have not been previously exposed, but are not otherwise associated with an “immune risk profile” predicting earlier mortality. Whether the accumulations of late-differentiated T cells driven primarily by CMV contribute to frailty and mortality or are only adaptive responses to the persistent virus remains controversial.

L. Muller

Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany e-mail: This email address is being protected from spam bots, you need Javascript enabled to view it

K. Hamprecht

Institute of Medical Virology, University of Tubingen, Tubingen, Germany e-mail: This email address is being protected from spam bots, you need Javascript enabled to view it

G. Pawelec (H)

Center for Medical Research, University of Tubingen,

Waldhornlestr. 22, 72072 Tubingen, Germany

Division of Cancer Studies, Faculty of Life Sciences and Medicine, King’s College London, London, UK

The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK e-mail: This email address is being protected from spam bots, you need Javascript enabled to view it © Springer International Publishing Switzerland 2017 V. Bueno et al. (eds.), The Ageing Immune System and Health, DOI 10.1007/978-3-319-43365-3_4

Either way, there is currently little direct evidence that “immunosenescence” contributes to either autoimmunity or cancer in the aged. This chapter reviews some of the studies implicating CMV infection in immunosenescence and its consequences for ageing trajectories in humans.


Ageing • Immune system • CMV • Immunosenescence • Health • Vaccination


CCR7 Chemokine receptor 7

CMV Cytomegalovirus

DC Dendritic cell

уб T cells Gamma-delta T cells

IE-1 Immediate early protein 1

IFN Interferon

KLRG Killer lectin-like cell receptor G1

MHC Major histocompatibility complex

NK cell Natural killer cell

PBMC Peripheral blood mononuclear cells pp65 Tegument protein

TLR Toll-like receptor

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