A glycoprotein endopeptidase enhances calcium influx and cytokine production by CD4+ T cells of old and young mice.
Many of the downstream signaling defects observed in aged T cells are believed to be the result of very early events involving the initial interaction between T cells and antigen-presenting cells. Recent findings suggest that this interaction is hindered by glycosylated surface macromolecules, including CD43, on the T cell surface. Treatment of CD4+ T cells by O-sialoglycoprotein endopeptidase (OSGE), which cleaves glycosylated forms of CD43, restores the ability of cells from aged mice to form immunological synapses and to express early activation markers. Here we show that OSGE enhances Ca2+ influx in T cells from CB6F1 mice, and enhances their ability to produce IL-2, IL-4, IL-5, IL-6, IL-10, IL-13 and IFNgamma at the mRNA level, and IL-2 and IFNgamma at the protein level, in the first 6 h after activation. Although OSGE has little effect on synapse formation in CD4+ T cells from young mice, our new data show that OSGE increases the production of most cytokines by young as well as old T cells. Secretion of the T(h)2 cytokine, IL-4, was altered only slightly by OSGE treatment, suggesting that the removal of OSGE-sensitive surface molecules may have differential effects on T(h)1 and T(h)2 cytokines. These data support a model in which O-glycosylated surface proteins inhibit CD4+ lymphocyte activation in both young and old mice, and in which such glycoproteins contribute to the age-related decline in cytokine production.
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA. bergers@umich.edu
Scott B
SB
Berger
Amir A
AA
Sadighi Akha
Richard A
RA
Miller
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006031:Glycosylation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D008565:Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase