Quantification of T-cell dynamics during latent cytomegalovirus infection in humans

Abstract

Cytomegalovirus (CMV) infection has a major impact on the T-cell pool, which is thought to be associated with ageing of the immune system. The effect on the T-cell pool has been interpreted as an effect of CMV on non-CMV specific T-cells. However, it remains unclear whether the effect of CMV could simply be explained by the presence of large, immunodominant, CMV-specific memory CD8+ T-cell populations. These have been suggested to establish through gradual accumulation of long-lived cells. However, little is known about their maintenance. We investigated the effect of CMV infection on T-cell dynamics in healthy older adults, and aimed to unravel the mechanisms of maintenance of large numbers of CMV-specific CD8+ T-cells. We studied the expression of senescence, proliferation, and apoptosis markers and quantified the in vivo dynamics of CMV-specific and other memory T-cell populations using in vivo deuterium labelling. Increased expression of late-stage differentiation markers by CD8+ T-cells of CMV+ versus CMV- individuals was not solely explained by the presence of large, immunodominant CMV-specific CD8+ T-cell populations. The lifespans of circulating CMV-specific CD8+ T-cells did not differ significantly from those of bulk memory CD8+ T-cells, and the lifespans of bulk memory CD8+ T-cells did not differ significantly between CMV- and CMV+ individuals. Memory CD4+ T-cells of CMV+ individuals showed increased expression of late-stage differentiation markers and decreased Ki-67 expression. Overall, the expression of senescence markers on T-cell populations correlated positively with their expected in vivo lifespan. Together, this work suggests that i) large, immunodominant CMV-specific CD8+ T-cell populations do not explain the phenotypical differences between CMV+ and CMV- individuals, ii) CMV infection hardly affects the dynamics of the T-cell pool, and iii) large numbers of CMV-specific CD8+ T-cells are not due to longer lifespans of these cells.

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

“…This is contributed by the existence of memory cells [ 38 ]. Immunologists regarded the long-lasting B-cells or T-cells as “memory cells.” Experiments gradually demonstrated that although the so-called “memory cells” are some specific forms of immune cells [ 39 , 40 ], they have similar half-lives as normal CD8+ cells [ 41 ]. Therefore, maintaining antibody levels in “memory cells” should be explained as a state of equilibrium between decay and regeneration.…”

Distinct Heterogeneity in the Naive T cell Compartments of Children and Adults

“…The prevalence of CMV infection correlates with age and significantly impact the T cell compartment. ( 16 , 17 ) To enable us to compare age-related changes with those induced by CMV infection, our cohort was equally balanced by age and CMV infection status. Large shifts in cell type composition were correlated with CMV infection status, as highlighted by increased proportion of effector populations.…”

Epigenetic quantification of immunosenescent CD8+ TEMRA cells in human blood

“…The frequent CMV activation induces antibodies and T‐cell clones to the virus, which are mostly of CD8 + EM and TEMRA origin (Fuchs et al, 2019 ). A recent study, however, showed that the changes in the T‐cell pool of CMV‐infected individuals cannot be explained by the presence of large numbers of CMV‐specific T‐cells suggesting that CMV infection may also affect the phenotype of non‐CMV specific CD8 + T‐cells (van den Berg et al, 2021 ).…”