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 Blood, 1 January 2009, Vol. 113, No. 1, pp. 95-99.
Prepublished online as a Blood First Edition Paper on October 9, 2008; DOI 10.1182/blood-2008-04-153262.

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IMMUNOBIOLOGY

Brief Report

A high-mobility, low-cost phenotype defines human effector-memory CD8+ T cells

Gabriela Zenhaeusern1, Patrick Gubser1, Petra Eisele2, Olivier Gasser3, Andrea Steinhuber4, Andrej Trampuz4, Christoph Handschin2, Andrew D. Luster5, and Christoph Hess1

1 Immunobiology Laboratory, University Hospital Basel, Basel, Switzerland; 2 Laboratory for Skeletal Muscle Biology, Institute of Physiology, University of Zurich, Zurich, Switzerland; 3 Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown; 4 Infectiology Laboratory, University Hospital Basel, Basel, Switzerland; and 5 Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown

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 1β [PGC-1β], estrogen-related receptor {alpha} [ERR{alpha}], 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.


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