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
PubMed publication date (edat): 7/1/2017
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.
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469909/