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dc.contributor.authorKato, Yu
dc.contributor.authorZaid, Ali
dc.contributor.authorDavey, Gayle M
dc.contributor.authorMueller, Scott N
dc.contributor.authorNutt, Stephen L
dc.contributor.authorZotos, Dimitra
dc.contributor.authorTarlinton, David M
dc.contributor.authorShortman, Ken
dc.contributor.authorLahoud, Mireille H
dc.contributor.authorHeath, William R
dc.contributor.authorCaminschi, Irina
dc.date.accessioned2018-04-27T03:48:10Z
dc.date.available2018-04-27T03:48:10Z
dc.date.issued2015
dc.identifier.issn0022-1767
dc.identifier.doi10.4049/jimmunol.1500767
dc.identifier.urihttp://hdl.handle.net/10072/171754
dc.description.abstractTargeting Ags to dendritic cell (DC) surface receptors can induce a variety of responses depending on the DC type targeted, the receptor targeted, and the adjuvant used. Clec9A (DNGR-1), which is expressed by CD8+ DCs, has been shown to bind F-actin exposed on damaged cells. Targeting Ag to this receptor in mice and nonhuman primates induces strong humoral immunity even in the absence of adjuvant, a process seen for a few select DC receptors. In contrast with other receptors, however, targeting Clec9A induces long-lived, affinity-matured Ab responses that are associated with efficient CD4+ T cell responses shown to possess properties of follicular Th cells (TFH). In this article, we provide definitive evidence that Clec9A targeting promotes the development of TFH by showing that responding CD4 T cells express CXCR5, PD1, the TFH transcription factor Bcl6, and the cytokine IL-21, and that these cells localize to germinal centers. Furthermore, we extend studies from the model Ag OVA to the viral Ag glycoprotein D of HSV-1 and examine the capacity of primed TFH to form functional memory. We show that targeting glycoprotein D to Clec9A even in the absence of adjuvant induced long-lived memory CXCR5+ PD1hi CD4+ T cells that proliferated extensively upon secondary challenge and rapidly developed into effector TFH. This was associated with enhanced germinal center B cell responses and accelerated Ab production. Our study indicates that targeting Ags to Clec9A in the absence of adjuvant routinely generates TFH responses that form long-lived memory capable of robust secondary TFH responses.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherAmerican Association of Immunologists
dc.publisher.place9650 Rockville Pike, Bethesda, MD 20814-3994
dc.relation.ispartofpagefrom1006
dc.relation.ispartofpageto1014
dc.relation.ispartofissue3
dc.relation.ispartofjournalJournal of Immunology
dc.relation.ispartofvolume195
dc.subject.fieldofresearchCellular Immunology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchcode110704
dc.subject.fieldofresearchcode1107
dc.titleTargeting Antigen to Clec9A Primes Follicular Th Cell Memory Responses Capable of Robust Recall
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
gro.hasfulltextNo Full Text
gro.griffith.authorZaid, Ali


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