UvA-DARE ( Digital Academic Repository ) CMV and immunosenescence : from basics to clinics (original) (raw)
Related papers
CMV and Immunosenescence: from basics to clinics
2012
Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16 th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
IMMUNITY & AGEING REVIEW CMV and Immunosenescence: from basics to clinics Open Access
2014
Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16 th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
Journal of General Virology, 2011
Human cytomegalovirus (CMV) establishes persistent, usually asymptomatic, infection in healthy people. Because CMV infection is associated with the presence of lower proportions of peripheral naïve CD8 + T-cells and a higher fraction of late-differentiated CD8 + cells, commonly taken as biomarkers of age-associated compromised adaptive immunity ('immunosenescence'), we asked whether chronic exposure to any persistent virus mediates these effects. Herpes simplex virus (HSV) is also a widespread herpesvirus that establishes lifelong persistence, but, unlike CMV, its impact on the distribution of T-cell subsets has not been established. Here, we analysed T-cell subsets in 93 healthy people aged 42-81 years infected or not infected with CMV and/or HSV. Individuals harbouring CMV were confirmed to possess lower frequencies of naïve CD8 + T-cells (defined as CD45RA + CCR7 + CD27 + CD28 + ) and greater proportions of late-differentiated effector memory (CD45RA " CCR7 " CD27 " CD28 " ) and so-called TEMRA (CD45RA + CCR7 " CD27 " CD28 " ) CD4 and CD8 subsets, independent of HSV seropositivity. In CMV-seronegative donors, HSV did not affect T-cell subset distribution significantly. We conclude that these hallmarks of age-associated alterations to immune signatures are indeed observed in the general population in people infected with CMV and not those infected with a different persistent herpesvirus.
Report from the second cytomegalovirus and immunosenescence workshop
Immunity & Ageing, 2011
The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4 th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.
New advances in CMV and immunosenescence
Experimental Gerontology, 2014
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of im-59 munological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is as-60 sociated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated in immunosenescence and in age-62 related diseases remains incomplete and many aspects of CMV involvement in immune aging remain controver-63 sial. The attendees of the 4th International Workshop on "CMV & Immunosenescence", held in Parma, Italy, 64 25-27th March, 2013, presented and discussed data related to these open questions, which are reported in 65 this commentary.
Immunity & Ageing, 2016
Background: Cytomegalovirus (CMV) is a highly prevalent herpesvirus, which maintains lifelong latency and places a significant burden on host immunity. Infection is associated with increased rates of vascular disease and overall mortality in the elderly and there is an urgent need for improved understanding of the viral-host balance during ageing. CMV is extremely difficult to detect in healthy donors, however, using droplet digital PCR of DNA from peripheral blood monocytes, we obtained an absolute quantification of viral load in 44 healthy donors across a range of ages. Results: Viral DNA was detected in 24 % (9/37) of donors below the age of 70 but was found in all individuals above this age. Furthermore, the mean CMV load was only 8.6 copies per 10,000 monocytes until approximately 70 years of age when it increased by almost 30 fold to 249 copies in older individuals (p < 0.0001). CMV was found within classical CD14+ monocytes and was not detectable within the CD14-CD16+ subset. The titre of CMV-specific IgG increased inexorably with age indicating that loss of humoral immunity is not a determinant of the increased viral load. In contrast, although cellular immunity to the structural late protein pp65 increased with age, the T cell response to the immediate early protein IE1 decreased in older donors. Conclusion: These data reveal that effective control of CMV is impaired during healthy ageing, most probably due to loss of cellular control of early viral reactivation. This information will be of value in guiding efforts to reduce CMV-associated health complications in the elderly.