Ex vivo enzymatic treatment of aged CD4 T cells restores antigen-driven CD69 expression and proliferation in mice

Abstract

Declines in immune function have been associated with declines in the function of naïve CD4 T cells. In vitro studies of naïve CD4 T cells in TCR-specific transgenic AND mice have shown age-related defects in immunosynapse formation, activation, proliferation and cytokine production. Previous work has also documented age-related alteration in the glycosylation of surface proteins involved in TCR signaling, and shown that enzymatic treatments to remove specific surface glycoproteins can restore in vitro function in CD4 cells from aged mice. Here an adoptive transfer system shows that a large percentage of naïve CD4 T cells from old mice fail to express CD69 and expand in antigen-primed mice, but these declines in CD69 and expansion can be restored by ex vivo pretreatment of the T cells with the bacterial enzyme O-sialoglycoprotein endopeptidase (OSGE). OSGE treatment also repairs the age-dependent loss of CD69 expression after in vivo activation.