Polysialylation is a general feature of immune activation

Sialic acids are critical regulators of immune responses and the sialic acid-Siglec axis has receive much attention recently for it role as a new immune checkpoint. While α2,3- and α2,6-linked sialosides have been well studied, much less is known about the α2,8-linked polysialic acid (polySia), especially in the adaptive immune system. We demonstrate here that polySia is actually found in all major classes of circulating immune cells, including B and T cells, where it is strongly associated with prior antigen exposure. Cell surface expression of polySia could be observed within 24 h of activation of naïve T cells but did not correlate with expression of the immune-specific polysialyltransferase ST8Sia4. Finally, we assessed the effects of smoking on polySia levels, and noted substantial increased levels of polySia, particularly on effector T cells and preferentially in males.