Cytomegalovirus Infection

Abstract

The human immune system evolved to defend the organism against pathogens, but is clearly less well able to do so in the elderly, resulting in greater morbidity and mortality due to infectious disease in old people, and higher healthcare costs. Many age-associated immune alterations have been reported over the years, of which probably the changes in T cell immunity, often manifested dramatically as large clonal expansions of cells of limited antigen specificity together with a marked shrinkage of the T cell antigen receptor repertoire, are the most notable. It has recently emerged that the common herpesvirus, cytomegalovirus (CMV), which establishes persistent, life-long infection, usually asymptomatically, may well be the driving force behind clonal expansions and altered phenotypes and functions of CD8 cells seen in most old people. In those few who are not CMV-infected, another even more common herpesvirus, the Epstein-Barr virus, appears to have the same effect. These virus-driven changes are less marked in "successfully aged" centenarians, but most marked in people whom longitudinal studies have shown to be at higher risk of death, that is, those possessing an "immune risk profile" (IRP) characterized by an inverted CD4:8 ratio (caused by the accumulation primarily of CD8(+) CD28(-) cells). These findings support the hypothesis that persistent herpesviruses, especially CMV, act as chronic antigenic stressors and play a major causative role in immunosenescence and associated mortality.

Functional Exhaustion of CD4+ T Lymphocytes during Primary Cytomegalovirus Infection

“…2 CMVspecific T cells accumulate slowly over time because of repetitive antigenic stimulation (36)(37)(38). Our results indicate that the differentiation of CMV-specific CD4 + T cells occurs early during the course of primary infection.…”

Persistent accumulation of interferon-γ-producing CD8+CD56+ T cells in blood from patients with coronary artery disease

“…It is unique amongst herpesviruses by inducing senescence in T cells involving features like enhanced expression of natural killer cell markers and lack of CD28 12 . Accordingly, we found increased proportions of CD8 + CD56 + T cells in CMV seropositive individuals although CMV seropositivity alone could not explain the expansion of the CD8 + CD56 + T cell subset in blood of CAD patients.…”

“…In infants, the numbers of circulating CD8 + CD56 + T cells are extremely low, but then increase with age 10 . The induction of CD56 has been shown to correlate with the loss of CD28, a hallmark of immunological aging [10][11] , and furthermore, the conversion to a senescent T cell phenotype is accentuated by a common pathogen, namely cytomegalovirus (CMV) 12 . In addition, increased proportions of circulating CD8 + CD56 + T cells are described in chronic autoimmune diseases like rheumatoid arthritis, sarcoidosis and…”

Recent advances in CMV tropism, latency, and diagnosis during aging

“…Chronic CMV infection is currently diagnosed by a positive anti-HCMV IgG serology, and is believed to contribute significantly to immunosenescence and adverse health outcomes in older adults (Pawelec et al 2005;Koch et al 2007;Schmaltz et al 2005;Wang et al 2010;Aiello et al 2008;Roberts et al 2010;Strandberg et al 2009). However, critical evaluation of the literature reveals the heterogeneity of HCMVseropositive older adult population and inconsistent findings.…”