Abstract
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.
MeSH terms
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Adenosine Triphosphate / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Calorimetry
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Carrier Proteins / genetics
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Cell Movement / immunology*
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Cytochromes c / genetics
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Energy Metabolism / immunology*
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Estrogen Receptor alpha / genetics
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Flow Cytometry / methods*
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Humans
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Immunologic Memory / immunology*
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Immunophenotyping / methods*
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Ion Channels / genetics
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L-Selectin / metabolism
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Mitochondrial Proteins / genetics
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Mitochondrial Proton-Translocating ATPases / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins
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Receptors, CCR7 / metabolism
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Uncoupling Protein 2
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Uncoupling Protein 3
Substances
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CCR7 protein, human
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Carrier Proteins
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Estrogen Receptor alpha
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Ion Channels
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Mitochondrial Proteins
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PPARGC1B protein, human
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RNA, Messenger
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RNA-Binding Proteins
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Receptors, CCR7
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UCP2 protein, human
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Uncoupling Protein 2
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Uncoupling Protein 3
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L-Selectin
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Adenosine Triphosphate
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Cytochromes c
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Mitochondrial Proton-Translocating ATPases