A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.

CD8(+) T cell memory inflation, first described in murine CMV (MCMV) infection, is characterized by the accumulation of high-frequency, functional Ag-specific CD8(+) T cell pools with an effector-memory phenotype and enrichment in peripheral organs. Although persistence of Ag is considered essential...

Full description

Bibliographic Details
Main Authors: Bolinger, B, Sims, S, O'Hara, G, de Lara, C, Tchilian, E, Firner, S, Engeler, D, Ludewig, B, Klenerman, P
Format: Journal article
Language:English
Published: 2013
_version_ 1826295387914240000
author Bolinger, B
Sims, S
O'Hara, G
de Lara, C
Tchilian, E
Firner, S
Engeler, D
Ludewig, B
Klenerman, P
author_facet Bolinger, B
Sims, S
O'Hara, G
de Lara, C
Tchilian, E
Firner, S
Engeler, D
Ludewig, B
Klenerman, P
author_sort Bolinger, B
collection OXFORD
description CD8(+) T cell memory inflation, first described in murine CMV (MCMV) infection, is characterized by the accumulation of high-frequency, functional Ag-specific CD8(+) T cell pools with an effector-memory phenotype and enrichment in peripheral organs. Although persistence of Ag is considered essential, the rules underpinning memory inflation are still unclear. The MCMV model is, however, complicated by the virus's low-level persistence and stochastic reactivation. We developed a new model of memory inflation based on a β-galactosidase (βgal)-recombinant adenovirus vector. After i.v. administration in C57BL/6 mice, we observed marked memory inflation in the βgal96 epitope, whereas a second epitope, βgal497, undergoes classical memory formation. The inflationary T cell responses show kinetics, distribution, phenotype, and functions similar to those seen in MCMV and are reproduced using alternative routes of administration. Memory inflation in this model is dependent on MHC class II. As in MCMV, only the inflating epitope showed immunoproteasome independence. These data define a new model for memory inflation, which is fully replication independent, internally controlled, and reproduces the key immunologic features of the CD8(+) T cell response. This model provides insight into the mechanisms responsible for memory inflation and, because it is based on a vaccine vector, also is relevant to novel T cell-inducing vaccines in humans.
first_indexed 2024-03-07T04:00:13Z
format Journal article
id oxford-uuid:c451444f-b4aa-40c5-973f-5551c86d65bd
institution University of Oxford
language English
last_indexed 2024-03-07T04:00:13Z
publishDate 2013
record_format dspace
spelling oxford-uuid:c451444f-b4aa-40c5-973f-5551c86d65bd2022-03-27T06:22:33ZA new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c451444f-b4aa-40c5-973f-5551c86d65bdEnglishSymplectic Elements at Oxford2013Bolinger, BSims, SO'Hara, Gde Lara, CTchilian, EFirner, SEngeler, DLudewig, BKlenerman, PCD8(+) T cell memory inflation, first described in murine CMV (MCMV) infection, is characterized by the accumulation of high-frequency, functional Ag-specific CD8(+) T cell pools with an effector-memory phenotype and enrichment in peripheral organs. Although persistence of Ag is considered essential, the rules underpinning memory inflation are still unclear. The MCMV model is, however, complicated by the virus's low-level persistence and stochastic reactivation. We developed a new model of memory inflation based on a β-galactosidase (βgal)-recombinant adenovirus vector. After i.v. administration in C57BL/6 mice, we observed marked memory inflation in the βgal96 epitope, whereas a second epitope, βgal497, undergoes classical memory formation. The inflationary T cell responses show kinetics, distribution, phenotype, and functions similar to those seen in MCMV and are reproduced using alternative routes of administration. Memory inflation in this model is dependent on MHC class II. As in MCMV, only the inflating epitope showed immunoproteasome independence. These data define a new model for memory inflation, which is fully replication independent, internally controlled, and reproduces the key immunologic features of the CD8(+) T cell response. This model provides insight into the mechanisms responsible for memory inflation and, because it is based on a vaccine vector, also is relevant to novel T cell-inducing vaccines in humans.
spellingShingle Bolinger, B
Sims, S
O'Hara, G
de Lara, C
Tchilian, E
Firner, S
Engeler, D
Ludewig, B
Klenerman, P
A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
title A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
title_full A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
title_fullStr A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
title_full_unstemmed A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
title_short A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
title_sort new model for cd8 t cell memory inflation based upon a recombinant adenoviral vector
work_keys_str_mv AT bolingerb anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT simss anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT oharag anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT delarac anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT tchiliane anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT firners anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT engelerd anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT ludewigb anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT klenermanp anewmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT bolingerb newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT simss newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT oharag newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT delarac newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT tchiliane newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT firners newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT engelerd newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT ludewigb newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector
AT klenermanp newmodelforcd8tcellmemoryinflationbaseduponarecombinantadenoviralvector