Distinct energy requirements for human memory CD4 T-cell homeostatic functions

Dennis D. Taub, Charles S. Hesdorffer, Luigi Ferrucci, Karen Madara, Janice B. Schwartz, Edward J. Goetzl

Research output: Contribution to journalArticlepeer-review

Abstract

Differentiation and activation of CD4 memory T cells (Tmem 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 Tmem 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 Tmem cells, altered FAO and glycolysis only minimally or not at all. Inhibition of CD4 Tmem-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 Tmem 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 Tmem cells increased their chemotaxis to CCL5, which was dependent predominantly on glycolysis rather than FAO. The sources supplying energy for diverse functions of unactivated Tmem cells differ from that required for function after immune activation.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalFASEB Journal
Volume27
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Adherence
  • Apoptosis
  • Chemotaxis
  • Fatty acid oxidation
  • Glycolysis
  • Immunosenescence

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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