title: Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes.
abstract: Cytotoxic T lymphocyte (CTL) senescence may be an important mechanism of immune failure in HIV-1 infection. We find that senescence of HIV-1-specific CTL clones causes loss of killing activity, preventable by transduction with telomerase. Furthermore, senescence is associated with reduced expression of the effector molecules granzyme and perforin, suggesting CTL "exhaustion" can result in hypofunction. These results agree with other studies showing that HIV-1-specific CTL exhibit abnormal phenotypes in vivo, and suggest the possibility that chronic turnover is an important mechanism of antiviral failure in HIV-1 infection.
authors.affiliation: Department of Medicine (Division of Infectious Diseases), UCLA Medical Center, Los Angeles, CA 90095-1688, USA. oyang@mednet.ucla.edu
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Holly
authors.initials: H
authors.lastname: Lin
authors.forename: Mirabelle
authors.initials: M
authors.lastname: Dagarag
authors.forename: Hwee L
authors.initials: HL
authors.lastname: Ng
authors.forename: Rita B
authors.initials: RB
authors.lastname: Effros
authors.forename: Christel H
authors.initials: CH
authors.lastname: Uittenbogaart
mesh_terms: D000375:Aging / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D002908:Chronic Disease; D053804:Granzymes; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases