Submitted April 21, 2008
Accepted August 5, 2008
A "high-mobility low-cost" phenotype defines human effector-memory CD8+ T-cells
Gabriela Zenhaeusern, Patrick Gubser, Petra Eisele, Olivier Gasser, Andrea Steinhuber, Andrej Trampuz, Christoph Handschin, Andrew D. Luster, and Christoph Hess*
Immunobiology Laboratory, University Hospital Basel, Basel, Switzerland
Laboratory for Skeletal Muscle Biology, Institute of Physiology, University of Zurich, Zurich, Switzerland
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
Infectiology Laboratory, University Hospital Basel, Basel, Switzerland
Center for Immunology and Inflammatory Disease, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
* Corresponding author; email: chess{at}uhbs.ch.
T-cells move randomly ('random-walk'), a characteristic thought to be integral to their function. Using migration-assays and time-lapse microscopy we found (i) that CD8+T-cells lacking the lymphnode homing receptors CCR7 and CD62L migrate more efficiently in transwell assays and (ii) 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 (PGC-1
, ERR
, Cytochrome C, ATP Synthase, and the uncoupling proteins UCP-2 and UCP-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 non-lymphoid vs. lymphoid homing CD8+T-cells.
