Age-related defects in CD4+ T cell activation reversed by glycoprotein endopeptidase

✍ Scribed by Gonzalo G. Garcia; Richard A. Miller

• Book ID: 102164039
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 259 KB
• Volume: 33
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200324310

✦ Synopsis

CD4(+) T cells from old mice show defects in the activation process including deficiency in the formation of immunosynapses with antigen-presenting cells. We show that CD4(+) T cells from old mice express unusually high levels of glycosylated forms of the bulky T cell glycoprotein CD43, particularly on a subset of functionally anergic cells expressing P-glycoprotein. T cells from old donors also show a decline in the association of CD43 with cytoskeletal matrix and in the proportion of T cells that can exclude CD43 from the synapse. O-sialoglycoprotein endopeptidase, which removes the external domain of CD43 and other O-sialoglycoproteins from the aged naive CD4(+) T cells of TCR-transgenic mice, restores early agonist-independent stages and later agonist-dependent stages of synapse formation as well as expression of the activation markers CD69 and CD25 to the levels found in the young mice. These data support a model in which O-glycosylated forms of T cell surface molecules, including CD43, are largely responsible for age-related defects in TCR signaling and function.