High Levels of CD244 Rather Than CD160 Associate With CD8+ T-Cell Aging

Abstract

Aging leads to functional dysregulation of the immune system, especially T cell defects. Previous studies have shown that the accumulation of co-inhibitory molecules plays an essential role in both T cell exhaustion and aging. In the present study, we showed that CD244 and CD160 were both up-regulated on CD8+ T cells of elderly individuals. CD244+CD160- CD8+ T cells displayed the increased activity of β-GAL, higher production of cytokines, and severe metabolic disorders, which were characteristics of immune aging. Notably, the functional dysregulation associated with aging was reversed by blocking CD244 instead of CD160. Meanwhile, CD244+CD160+ CD8+ T cells exhibited features of exhaustion, including lower levels of cytokine, impaired proliferation, and intrinsic transcriptional regulation, compared to CD244+CD160- population. Collectively, our findings demonstrated that CD244 rather than CD160 acts as a prominent regulator involved in T cell aging, providing a solid therapeutic target to improve disorders and comorbidities correlated to immune system aging.

The cell cycle regulator p16 promotes tumor infiltrated CD8+ T cell exhaustion and apoptosis

“…Previous studies have indicated that senescent T cells typically exhibit increased cell size and granularity [ 29 ], along with reduced expression of effector molecules such as GzmB and perforin [ 29 ]. Additionally, several studies have suggested that aged human T cells may consist of various distinct populations [ 30 – 33 ]. For instance, the CD8 + CD28 − T cells and effector memory T cells expressing CD45RA (Temra) cells have been shown to exhibit activation of p38 mitogen-activated protein kinase (MAPK), secretion of senescence-associated secretory phenotype (SASP), phosphorylation of γ-H2AX, and expression of surface markers associated with senescence such as KLRG1 [ 30 , 31 , 34 ].…”

Optimal combination of MYCN differential gene and cellular senescence gene predicts adverse outcomes in patients with neuroblastoma

“…CD244 (2B4) binding to the ligand CD48 has been found to be a signaling pathway for co-stimulation or negative regulation of multiple immune cells in tumor, that currently considered to be an important marker of immune cell senescence ( 47 , 48 ). CD244+ CD8+ aging T cells exhibited features of exhaustion, including lower levels of cytokine, impaired proliferation, and intrinsic transcriptional regulation ( 49 ). Phenotype analysis showed that the proportion of CD8+ T cells did not increase after PBMC exposure to SK-N-BE (2) tumor antigen as it did after exposure to SH-SY5Y tumor antigen.…”

A signature of pre-operative biomarkers of cellular senescence to predict risk of cardiac and kidney adverse events after cardiac surgery

“…Briefly, CD28 and LAG3 are established markers of T cell exhaustion 12,13 . CD244 was first described as an exhaustion marker and has also been shown to correlate with age-dependent impairment of T cells 14 ; however, more recently it was shown to regulate autophagy 15 , an important process that may also involve p14 16 . Finally, suPAR has been shown to be secreted by senescent cells 17,18 ; it is an immune-derived pathogenic factor of kidney disease and potentially cardiovascular disease 19,20 .…”