Article: article from journal or magazin.
A high-mobility, low-cost phenotype defines human effector-memory CD8+ T cells.
Publication types: Journal Article
T cells move randomly ("random-walk"), a characteristic thought to be integral to their function. Using migration assays and time-lapse microscopy, we found that CD8+ T cells lacking the lymph node homing receptors CCR7 and CD62L migrate more efficiently in transwell assays, and that these same cells are characterized by a high frequency of cells exhibiting random crawling activity under culture conditions mimicking the interstitial/extravascular milieu, but not when examined on endothelial cells. To assess the energy efficiency of cells crawling at a high frequency, we measured mRNA expression of genes key to mitochondrial energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1beta [PGC-1beta], estrogen-related receptor alpha [ERRalpha], cytochrome C, ATP synthase, and the uncoupling proteins [UCPs] UCP-2 and -3), quantified ATP contents, and performed calorimetric analyses. Together these assays indicated a high energy efficiency of the high crawling frequency CD8+ T-cell population, and identified differentially regulated heat production among nonlymphoid versus lymphoid homing CD8+ T cells.
Adenosine Triphosphate/metabolism, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Calorimetry, Carrier Proteins/genetics, Cell Movement/immunology, Cytochromes c/genetics, Energy Metabolism/immunology, Estrogen Receptor alpha/genetics, Flow Cytometry/methods, Humans, Immunologic Memory/immunology, Immunophenotyping/methods, Ion Channels/genetics, L-Selectin/metabolism, Mitochondrial Proteins/genetics, Mitochondrial Proton-Translocating ATPases/genetics, RNA, Messenger/metabolism, Receptors, CCR7/metabolism
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