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

• Published in: Blood 2009-01, Vol.113 (1), p.95-99
• Main Authors: Zenhaeusern, Gabriela, Gubser, Patrick, Eisele, Petra, Gasser, Olivier, Steinhuber, Andrea, Trampuz, Andrej, Handschin, Christoph, Luster, Andrew D., Hess, Christoph
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Biological and medical sciences; Calorimetry; Carrier Proteins - genetics; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Movement - immunology; Cytochromes c - genetics; Energy Metabolism - immunology; Estrogen Receptor alpha - genetics; Flow Cytometry - methods; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunologic Memory - immunology; Immunophenotyping - methods; Ion Channels - genetics; L-Selectin - metabolism; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mitochondrial Proteins - genetics; Mitochondrial Proton-Translocating ATPases - genetics; Receptors, CCR7 - metabolism; RNA, Messenger - metabolism; RNA-Binding Proteins; Uncoupling Protein 2; Uncoupling Protein 3
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-04-153262

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 γ coactivator 1β [PGC-1β], estrogen-related receptor α [ERRα], 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.