title: Distinct energy requirements for human memory CD4 T-cell homeostatic functions.
abstract: Differentiation and activation of CD4 memory T cells (T(mem) cells) require energy from different sources, but little is known about energy sources for maintenance and surveillance activities of unactivated T(mem) cells. Mitochondrial fatty acid oxidation (FAO) in human unactivated CD4 T(mem) cells was significantly enhanced by inhibition of glycolysis, with respective means of 1.7- and 4.5-fold for subjects <45 yr and >65 yr, and by stimulation of AMP-activated protein kinase, with respective means of 1.3- and 5.2-fold. However, CCL19 and sphingosine 1-phosphate (S1P), which control homeostatic lymphoid trafficking of unactivated T(mem) cells, altered FAO and glycolysis only minimally or not at all. Inhibition of CD4 T(mem)-cell basal FAO, but not basal glycolysis, significantly suppressed CCL19- and S1P-mediated adherence to collagen by >50 and 20%, respectively, and chemotaxis by >20 and 50%. Apoptosis of unactivated T(mem) cells induced by IL-2 deprivation or CCL19 was increased significantly by >150 and 70%, respectively, with inhibition of FAO and by >110 and 30% with inhibition of glycolysis. Anti-TCR antibody activation of T(mem) cells increased their chemotaxis to CCL5, which was dependent predominantly on glycolysis rather than FAO. The sources supplying energy for diverse functions of unactivated T(mem) cells differ from that required for function after immune activation.
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hesdorffer
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Karen
authors.initials: K
authors.lastname: Madara
authors.forename: Janice B
authors.initials: JB
authors.lastname: Schwartz
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Goetzl
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D054415:Chemokine CCL19 / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D008246:Lysophospholipids / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C515460:CCL19 protein, human; D054415:Chemokine CCL19; D005227:Fatty Acids; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine