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

First Author  Garcia GG Year  2003
Journal  Eur J Immunol Volume  33
Issue  12 Pages  3464-72
PubMed ID  14635057 Mgi Jnum  J:90603
Mgi Id  MGI:3044274 Doi  10.1002/eji.200324310
Citation  Garcia GG, et al. (2003) Age-related defects in CD4+ T cell activation reversed by glycoprotein endopeptidase. Eur J Immunol 33(12):3464-72
abstractText  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.
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