title: A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector.
abstract: 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.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, United Kingdom.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bolinger
authors.forename: Stuart
authors.initials: S
authors.lastname: Sims
authors.forename: Geraldine
authors.initials: G
authors.lastname: O'Hara
authors.forename: Catherine
authors.initials: C
authors.lastname: de Lara
authors.forename: Elma
authors.initials: E
authors.lastname: Tchilian
authors.forename: Sonja
authors.initials: S
authors.lastname: Firner
authors.forename: Daniel
authors.initials: D
authors.lastname: Engeler
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D007156:Immunologic Memory / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D011994:Recombinant Proteins