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Antigen-specific activation thresholds of CD8+ T cells are independent of IFN-I-mediated partial lymphocyte activation

Wijesundara, Danushka; Kumar, Sheetal; Alsharifi, Mohammed; Mullbacher, Arno; Regner, Matthias

Description

Type-I IFN (IFN-I) are highly pleiotropic cytokines known to modulate immune responses and play an early central role in mediating antiviral defenses. We have shown that IFN-I mediate transient up-regulation of a distinct subset of lymphocyte surface activation markers on both B and T cells in vivo independent of cognate antigen: a state referred to as 'partial lymphocyte activation'. Here we investigated in vitro the possibility that partial lymphocyte activation may serve to lower the...[Show more]

dc.contributor.authorWijesundara, Danushka
dc.contributor.authorKumar, Sheetal
dc.contributor.authorAlsharifi, Mohammed
dc.contributor.authorMullbacher, Arno
dc.contributor.authorRegner, Matthias
dc.date.accessioned2015-12-10T21:57:41Z
dc.identifier.issn0953-8178
dc.identifier.urihttp://hdl.handle.net/1885/39886
dc.description.abstractType-I IFN (IFN-I) are highly pleiotropic cytokines known to modulate immune responses and play an early central role in mediating antiviral defenses. We have shown that IFN-I mediate transient up-regulation of a distinct subset of lymphocyte surface activation markers on both B and T cells in vivo independent of cognate antigen: a state referred to as 'partial lymphocyte activation'. Here we investigated in vitro the possibility that partial lymphocyte activation may serve to lower the antigen-specific activation thresholds for T cells. We found that the kinetics of Ca2+ flux in T cells responding to TCR cross-linking was not enhanced in partially activated T cells. Furthermore, following TCR stimulation with anti-cluster of differentiation (CD) 3ε, a lower proportion of partially activated than naive T cells proliferated. In contrast, the proliferation of partially activated and naive ovalbumin peptide (OVAp, SIINFEKL) specific CD8+ T cells (OT-I CD8+ T cells) was similar when stimulated with OVAp. Surprisingly, using an enzyme-linked immunospot (ELISPOT) assay for IFN-γ secretion, we found that a higher number of partially activated OT-I CD8+ T cells expressed effector functions than did naive OT-I CD8+ T cells. This is most readily explained by an increased survival of activated antigen-specific CD8+ T cells from a pool of partially activated T cells than naive T cells. Overall, when examining the effects of early (Ca2+ flux), intermediate (proliferation) or late events (IFN-γ secretion) of T-cell activation, we found that partial activation promotes the survival but does not alter the antigen-specific activation thresholds of CD8+ T cells.
dc.publisherOxford University Press
dc.sourceInternational Immunology
dc.subjectKeywords: calcium ion; CD69 antigen; CD86 antigen; gamma interferon; interferon; ovalbumin; polyclonal antibody; T lymphocyte receptor; animal cell; animal experiment; antigen specificity; article; CD25+ T lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; cell diff Ca2+; IFN; IFN-?; Proliferation; R-IFN-ß
dc.titleAntigen-specific activation thresholds of CD8+ T cells are independent of IFN-I-mediated partial lymphocyte activation
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume22
dc.date.issued2010
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.ariespublicationu4020362xPUB185
local.type.statusPublished Version
local.contributor.affiliationWijesundara, Danushka, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKumar, Sheetal, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationAlsharifi, Mohammed, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMullbacher, Arno, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRegner, Matthias, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue9
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage11
local.identifier.doi10.1093/intimm/dxq064
dc.date.updated2016-02-24T10:27:07Z
local.identifier.scopusID2-s2.0-77956140880
local.identifier.thomsonID000281344800005
CollectionsANU Research Publications

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