A high-mobility, low-cost phenotype defines human effector-memory CD8+ T cells.
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.
Immunobiology Laboratory, Department of Biomedicine, University Hospital Basel, 20 Hebelstrasse, Basel, Switzerland.
Gabriela
G
Zenhaeusern
Patrick
P
Gubser
Petra
P
Eisele
Olivier
O
Gasser
Andrea
A
Steinhuber
Andrej
A
Trampuz
Christoph
C
Handschin
Andrew D
AD
Luster
Christoph
C
Hess
D000255:Adenosine Triphosphate / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002151:Calorimetry; D002352:Carrier Proteins / Q000235:genetics; D002465:Cell Movement / Q000276:immunology*; D045304:Cytochromes c / Q000235:genetics; D004734:Energy Metabolism / Q000276:immunology*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping / Q000379:methods*; D007473:Ion Channels / Q000235:genetics; D019041:L-Selectin / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D054400:Receptors, CCR7 / Q000378:metabolism; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
C515370:CCR7 protein, human; D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D007473:Ion Channels; D024101:Mitochondrial Proteins; C455622:PPARGC1B protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D054400:Receptors, CCR7; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D019041:L-Selectin; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D025261:Mitochondrial Proton-Translocating ATPases