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Distinct energy requirements for human memory CD4 T‐cell homeostatic functions
Author(s) -
Taub Dennis D.,
Hesdorffer Charles S.,
Ferrucci Luigi,
Madara Karen,
Schwartz Janice B.,
Goetzl Edward J.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-217620
Subject(s) - glycolysis , ccl19 , microbiology and biotechnology , biology , immunosurveillance , immune system , cancer research , chemistry , biochemistry , immunology , chemokine , metabolism , chemokine receptor
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.—Taub, D. D., Hesdorffer, C. S., Ferrucci, L., Madara, K., Schwartz, J. B., Goetzl, E. J. Distinct energy requirements for human memory CD4 T‐cell homeostatic functions. FASEB J. 27, 342–349 (2013). www.fasebj.org