Longevity & AgingAging Strips CD8 T Cells of a Key Sugar Coat, Blunting Immune Defense
As mice age, CD8+ T cells progressively lose α2,6-linked sialic acid from their surface glycocalyx. This change is driven by an accumulation of effector T cells that naturally lack this sugar modification. Researchers deleted the sialyltransferase gene St6gal1 specifically in T cells to model this loss, revealing that α2,6-sialic acid is essential for maintaining naïve T cell responsiveness. St6gal1-deficient mice showed impaired clearance of Listeria monocytogenes and worse tumor control. Checkpoint blockade with anti-PD-1 partially restored antitumor immunity in these mice, suggesting the glycocalyx intersects with inhibitory signaling pathways. The findings identify glycan remodeling as a novel mechanism underlying age-associated immune decline.
