Show simple item record Ferrari, Guido en_US 2011-06-21T17:32:22Z 2011-06-21T17:32:22Z 2010 en_US
dc.identifier.citation Makedonas,George;Hutnick,Natalie;Haney,Danielle;Amick,Alexandra C.;Gardner,Jay;Cosma,Gabriela;Hersperger,Adam R.;Dolfi,Douglas;Wherry,E. John;Ferrari,Guido;Betts,Michael R.. 2010. Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8(+) T Cells. Plos Pathogens 6(3): e1000798-e1000798. en_US
dc.identifier.issn 1553-7366 en_US
dc.description.abstract The prevailing paradigm of T lymphocyte control of viral replication is that the protective capacity of virus-specific CD8(+) T cells is directly proportional to the number of functions they can perform, with IL-2 production capacity considered critical. Having recently defined rapid perforin upregulation as a novel effector function of antigen-specific CD8(+) T cells, here we sought to determine whether new perforin production is a component of polyfunctional CD8(+) T cell responses that contributes to the control of several human viral infections: cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza (flu), and adenovirus (Ad). We stimulated normal human donor PBMC with synthetic peptides whose amino acid sequences correspond to defined CTL epitopes in the aforementioned viruses, and then used polychromatic flow cytometry to measure the functional capacity and the phenotype of the responding CD8(+) T cells. While EBV and flu-specific CD8(+) T cells rarely upregulate perforin, CMV-specific cells often do and Ad stimulates an exceptionally strong perforin response. The differential propensity of CD8(+) T cells to produce either IL-2 or perforin is in part related to levels of CD28 and the transcription factor T-bet, as CD8(+) T cells that rapidly upregulate perforin harbor high levels of T-bet and those producing IL-2 express high amounts of CD28. Thus, "polyfunctional'' profiling of antigen-specific CD8(+) T cells must not be limited to simply the number of functions the cell can perform, or one particular memory phenotype, but should actually define which combinations of memory markers and functions are relevant in each pathogenic context. en_US
dc.language.iso en_US en_US
dc.relation.isversionof doi:10.1371/journal.ppat.1000798 en_US
dc.subject epstein-barr-virus en_US
dc.subject hepatitis-c virus en_US
dc.subject transcription factor en_US
dc.subject lineage en_US
dc.subject commitment en_US
dc.subject immune-responses en_US
dc.subject b-virus en_US
dc.subject memory en_US
dc.subject effector en_US
dc.subject bet en_US
dc.subject lymphocytes en_US
dc.subject infectious diseases en_US
dc.subject microbiology en_US
dc.subject parasitology en_US
dc.subject virology en_US
dc.title Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8(+) T Cells en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US 2010-3-0 en_US
duke.description.endpage e1000798 en_US
duke.description.issue 3 en_US
duke.description.startpage e1000798 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Pathogens en_US

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