title: Mitochondrial potential and reactive oxygen intermediates in antigen-specific CD8+ T cells during viral infection.
abstract: Following many viral infections, there are large expansions of Ag-specific CD8(+) T cells. After viral clearance, mechanisms exist to ensure that the vast majority of effector cells undergo apoptosis. In studies of thymocyte apoptosis, loss of mitochondrial potential (deltapsi(m)) and excess production of reactive oxygen intermediates have been implicated as key events in cellular apoptosis. The purpose of the experiments presented in this work was to determine these parameters in Ag-specific CD8(+) T cells during a physiological response such as viral infection. Using lymphocytic choriomeningitis virus infection of mice, we found that Ag-specific CD8(+) effector T cells that had undergone recent TCR stimulation had an increased deltapsi(m). These cells also had increased levels of superoxide. As these cells progressed through the contraction of the immune response, their potential decreased, but superoxide levels remained similar to naive cells. One of the consequences of reduced mitochondrial potential is membrane permeability and subsequent caspase activation. We examined both the enzymatic activity and levels of cleaved caspase 3, an effector caspase, and could only detect increased levels in Ag-specific CD8(+) T cells on day 5 postinfection, a time point in which virus was still present. This contrasts with Ag-specific effector cells examined during the contraction phase that had no detectable caspase activity directly ex vivo. These data suggest that the apoptotic program begins earlier than previously expected on day 5, during the expansion phase.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. jgrayson@wfubmc.edu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Grayson
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Laniewski
authors.forename: J Gibson
authors.initials: JG
authors.lastname: Lanier
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000235:genetics; D007425:Intracellular Membranes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D017382:Reactive Oxygen Species; D020169:Caspases