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Immune Checkpoint Function of CD85j in CD8 T Cell Differentiation and Aging.


Maximus Peto’s Commentary

This inhibition of CD85j seems like it may be “messing with metabolism”, rather than addressing a persistent, underling damage/problem. However, their suggestion that CD85j is a marker of a population of senescent effector CD8 T cells, might be interesting to some readers on this distribution list.


Immune Checkpoint Function of CD85j in CD8 T Cell Differentiation and Aging.
Front Immunol. 2017 Jun 14;8:692.
Gustafson CE, Qi Q, Hutter-Saunders J, Gupta S, Jadhav R, Newell E, Maecker H, Weyand CM, Goronzy JJ
DOI: 10.3389/fimmu.2017.00692
PubMed publication date (edat): 7/1/2017

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.

PMID: 28659925
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469909/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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