Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies

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dc.contributor.authorRollman, Erik
dc.contributor.authorSmith, Miranda Z.
dc.contributor.authorBrooks, Andrew G.
dc.contributor.authorPurcell, Damian F J
dc.contributor.authorZuber, Bartek
dc.contributor.authorRamshaw, Ian
dc.contributor.authorKent, Stephen J
dc.date.accessioned2015-12-07T22:47:36Z
dc.date.issued2007
dc.date.updated2015-12-07T11:52:36Z
dc.description.abstractBoth the magnitude and function of vaccine-induced HIV-specific CD8 + CTLs are likely to be important in the outcome of infection. We hypothesized that rapid cytolysis by CTLs may facilitate control of viral challenge. Release kinetics of the cytolytic effector molecules granzyme B and perforin, as well as the expression of the degranulation marker CD107a and IFN-γ were simultaneously studied in SIV Gag164-172 KP9-specific CD8+ T cells from Mane-A*10+ pigtail macaques. Macaques were vaccinated with either prime-boost poxvirus vector vaccines or live-attenuated SIV vaccines. Prime-boost vaccination induced Gag-specific CTLs capable of only slow (after 3 h) production of IFN-γ and with limited (<5%) degranulation and granzyme B release. Vaccination with live-attenuated SIV resulted in a rapid cytolytic profile of SIV-specific CTLs with rapid (<0.5 h) and robust (>50% of tetramer-positive CD8+ T cells) degranulation and granzyme B release. The cytolytic phenotype following live-attenuated SIV vaccinations were similar to that associated with the partial resolution of viremia following SIVmac251 challenge of prime-boost-vaccinated macaques, albeit with less IFN-γ expression. High proportions of KP9-specific T cells expressed the costimulatory molecule CD28 when they exhibited a rapid cytolytic phenotype. The delayed cytolytic phenotype exhibited by standard vector-based vaccine-induced CTLs may limit the ability of T cell-based HIV vaccines to rapidly control acute infection following a pathogenic lentiviral exposure.
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/26134
dc.publisherAmerican Association of Immunologists
dc.sourceJournal of Immunology
dc.subjectKeywords: cell marker; gamma interferon; granzyme B; Human immunodeficiency virus vaccine; live vaccine; lysosome associated membrane protein 1; perforin; animal cell; animal experiment; animal model; article; CD8+ T lymphocyte; cell differentiation; cell killing;
dc.titleKilling Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies
dc.typeJournal article
local.bibliographicCitation.lastpage4579
local.bibliographicCitation.startpage4571
local.contributor.affiliationRollman, Erik, University of Melbourne
local.contributor.affiliationSmith, Miranda Z., University of Melbourne
local.contributor.affiliationBrooks, Andrew G., University of Melbourne
local.contributor.affiliationPurcell, Damian F J, University of Melbourne
local.contributor.affiliationZuber, Bartek, Mabtech
local.contributor.affiliationRamshaw, Ian, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKent, Stephen J, University of Melbourne
local.contributor.authoremailrepository.admin@anu.edu.au
local.contributor.authoruidRamshaw, Ian, u8202754
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.ariespublicationu6800332xPUB42
local.identifier.citationvolume179
local.identifier.scopusID2-s2.0-42049086137
local.identifier.uidSubmittedByu6800332
local.type.statusPublished Version

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