Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.

2.50
Hdl Handle:
http://hdl.handle.net/10033/311079
Title:
Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.
Authors:
Trsan, Tihana; Busche, Andreas; Abram, Maja; Wensveen, Felix M; Lemmermann, Niels A; Arapovic, Maja; Babic, Marina; Tomic, Adriana; Golemac, Mijo; Brinkmann, Melanie M; Jäger, Wiebke; Oxenius, Annette; Polic, Bojan; Krmpotic, Astrid; Messerle, Martin; Jonjic, Stipan
Abstract:
Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.
Affiliation:
Research group viral immune modulation, Helmholtz Centre for infection research, Braunschweig, Germany
Citation:
Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ. 2013, 110 (41):16550-5 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
8-Oct-2013
URI:
http://hdl.handle.net/10033/311079
DOI:
10.1073/pnas.1310215110
PubMed ID:
24052528
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
publications of the research group viral immunomodulation (VIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorTrsan, Tihanaen
dc.contributor.authorBusche, Andreasen
dc.contributor.authorAbram, Majaen
dc.contributor.authorWensveen, Felix Men
dc.contributor.authorLemmermann, Niels Aen
dc.contributor.authorArapovic, Majaen
dc.contributor.authorBabic, Marinaen
dc.contributor.authorTomic, Adrianaen
dc.contributor.authorGolemac, Mijoen
dc.contributor.authorBrinkmann, Melanie Men
dc.contributor.authorJäger, Wiebkeen
dc.contributor.authorOxenius, Annetteen
dc.contributor.authorPolic, Bojanen
dc.contributor.authorKrmpotic, Astriden
dc.contributor.authorMesserle, Martinen
dc.contributor.authorJonjic, Stipanen
dc.date.accessioned2014-01-08T15:40:39Z-
dc.date.available2014-01-08T15:40:39Z-
dc.date.issued2013-10-08-
dc.identifier.citationSuperior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ. 2013, 110 (41):16550-5 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn1091-6490-
dc.identifier.pmid24052528-
dc.identifier.doi10.1073/pnas.1310215110-
dc.identifier.urihttp://hdl.handle.net/10033/311079-
dc.description.abstractDue to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.en
dc.language.isoenen
dc.rightsArchived with thanks to Proceedings of the National Academy of Sciences of the United States of Americaen
dc.subject.meshAnimalsen
dc.subject.meshCD8-Positive T-Lymphocytesen
dc.subject.meshCytomegalovirusen
dc.subject.meshFlow Cytometryen
dc.subject.meshGenetic Vectorsen
dc.subject.meshImmune Evasionen
dc.subject.meshListeria monocytogenesen
dc.subject.meshMembrane Proteinsen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshNK Cell Lectin-Like Receptor Subfamily Ken
dc.subject.meshStatistics, Nonparametricen
dc.subject.meshVaccines, Syntheticen
dc.titleSuperior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.en
dc.typeArticleen
dc.contributor.departmentResearch group viral immune modulation, Helmholtz Centre for infection research, Braunschweig, Germanyen
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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