Age-related defects in CD4+ T cell activation reversed by glycoprotein endopeptidase.
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.
Garcia
Gonzalo G
GG
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, USA.
Miller
Richard A
RA
D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D006031:Glycosylation; D037181:Lectins, C-Type; D051917:Leukosialin; D008213:Lymphocyte Activation; D008666:Metalloendopeptidases / Q000494:pharmacology*; D051379:Mice; D020033:Protein Isoforms; D021381:Protein Transport; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D051917:Leukosialin; D008666:Metalloendopeptidases; D020033:Protein Isoforms; D015375:Receptors, Interleukin-2; D012795:Sialoglycoproteins; D000099192:CD69 Antigens; C497863:Spn protein, mouse; C070738:O-sialoglycoprotein endopeptidase