Enhancement of CD8 T-cell function through modifying surface glycoproteins in young and old mice.
Previous work from our laboratory has shown that modifying cell surface glycosylation with either a Clostridium perfringens-derived sialidase (CP-Siase), or an O-linked glycoprotein endopeptidase (OSGE) can enhance the function of CD4 T cells from both young and old mice at multiple levels. Here we have re-assessed the effect of age on CD8 T-cell function, and examined the outcome of enzymatic treatment with CP-Siase and OSGE on its different aspects. Pre-treatment of CD8 T cells with either CP-Siase or OSGE led to a significant increase in anti-CD3-mediated Ca2+ response in both young and old mice. Pre-treated CD8 T cells from both age groups also displayed a significant increase in activation-induced CD69 and CD25 expression, and produced significantly higher amounts of interleukin-2 and interferon-gamma in comparison to their untreated counterparts. Furthermore, pretreatment with either enzyme enhanced granzyme B expression in CD8 T cells, and increased their cytolytic activity in vitro. These data support the notion that glycosylated surface proteins hinder CD8 T-cell activation and function in both young and old mice, and raise the possibility of significantly improving CD8 T cell function in older individuals through enzymatic alteration of surface glycoproteins.
Sadighi Akha
Amir A
AA
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA. asadighi@umich.edu
Berger
Scott B
SB
Miller
Richard A
RA
D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006031:Glycosylation; D053804:Granzymes; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D002118:Calcium; D053804:Granzymes; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008666:Metalloendopeptidases; D009439:Neuraminidase; D015375:Receptors, Interleukin-2; D012697:Serine Endopeptidases; D000099192:CD69 Antigens; C509214:Gzmb protein, mouse; C070738:O-sialoglycoprotein endopeptidase