Sialic Acid Ligands of CD28 Suppress Costimulation of T Cells

Effector T cells
comprise the cellular arm of the adaptive immune
system and are essential for mounting immune responses against pathogens
and cancer. To reach effector status, costimulation through CD28 is
required. Here, we report that sialic acid-containing glycans on the
surface of both T cells and APCs are alternative ligands of CD28 that
compete with binding to its well-documented activatory ligand CD80
on the APC, resulting in attenuated costimulation. Removal of sialic
acids enhances antigen-mediated activation of naïve T cells
and also increases the revival of effector T cells made hypofunctional
or exhausted via chronic viral infection. This occurs through a mechanism
that is synergistic with antibody blockade of the inhibitory PD-1
axis. These results reveal a previously unrecognized role of sialic
acid ligands in attenuation of CD28-mediated costimulation of T cells.