Claire E. Gustafson, Qian Qi, Jessica Hutter-Saunders, Sheena Gupta, Rohit Jadhav, Evan Newell, Holden Maecker, Cornelia M. Weyand, Jörg J. Goronzy
Abstract
Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging. Here, we show that CD85j is mainly expressed by terminally differentiated effector (TEMRAs) CD8 T cells, which increase with age, in cytomegalovirus (CMV) infection and in males. CD85j(+) CMV-specific cells demonstrate clonal expansion. However, TCR diversity is similar between CD85j(+) and CD85j(-) compartments, suggesting that CD85j does not directly impact the repertoire of antigen-specific cells. Further phenotypic and functional analyses revealed that CD85j identifies a specific subset of CMV-responsive CD8 T cells that coexpress a marker of senescence (CD57) but retain polyfunctional cytokine production and expression of cytotoxic mediators. Blocking CD85j binding enhanced proliferation of CMV-specific CD8 T cells upon antigen stimulation but did not alter polyfunctional cytokine production. Taken together, these data demonstrate that CD85j characterizes a population of "senescent," but not exhausted antigen-specific effector CD8 T cells and indicates that CD85j is an important checkpoint regulator controlling expansion of virus-specific T cells during aging. Inhibition of CD85j activity may be a mechanism to promote stronger CD8 T cell effector responses during immune aging.
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 October 2018.
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#8,861,975
of 26,184,649 outputs
Outputs from Frontiers in immunology
#11,277
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#129,580
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Outputs of similar age from Frontiers in immunology
#170
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Altmetric has tracked 26,184,649 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 33,037 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has gotten more attention than average, scoring higher than 64% of its peers.
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We're also able to compare this research output to 385 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
