In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2021-12-16), p. e1010152-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010152
DOI:
10.1371/journal.ppat.1010152.g001
DOI:
10.1371/journal.ppat.1010152.g002
DOI:
10.1371/journal.ppat.1010152.g003
DOI:
10.1371/journal.ppat.1010152.g004
DOI:
10.1371/journal.ppat.1010152.g005
DOI:
10.1371/journal.ppat.1010152.g006
DOI:
10.1371/journal.ppat.1010152.t001
DOI:
10.1371/journal.ppat.1010152.t002
DOI:
10.1371/journal.ppat.1010152.s001
DOI:
10.1371/journal.ppat.1010152.s002
DOI:
10.1371/journal.ppat.1010152.s003
DOI:
10.1371/journal.ppat.1010152.s004
DOI:
10.1371/journal.ppat.1010152.s005
DOI:
10.1371/journal.ppat.1010152.s006
DOI:
10.1371/journal.ppat.1010152.s007
DOI:
10.1371/journal.ppat.1010152.s008
DOI:
10.1371/journal.ppat.1010152.s009
DOI:
10.1371/journal.ppat.1010152.s010
DOI:
10.1371/journal.ppat.1010152.s011
DOI:
10.1371/journal.ppat.1010152.s012
DOI:
10.1371/journal.ppat.1010152.s013
DOI:
10.1371/journal.ppat.1010152.r001
DOI:
10.1371/journal.ppat.1010152.r002
DOI:
10.1371/journal.ppat.1010152.r003
DOI:
10.1371/journal.ppat.1010152.r004
DOI:
10.1371/journal.ppat.1010152.r005
DOI:
10.1371/journal.ppat.1010152.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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