title: CD8+ T-cell expansion and maintenance after recombinant adenovirus immunization rely upon cooperation between hematopoietic and nonhematopoietic antigen-presenting cells.
abstract: We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon persistent transgene expression beyond the peak of the response. In this report, we have further investigated the location and nature of the cell populations responsible for this sustained response. The draining lymph nodes were found to be important for primary expansion but not for memory maintenance, suggesting that antigen presentation through a nonlymphoid source was required. Using bone marrow chimeric mice, we determined that antigen presentation by nonhematopoietic antigen-presenting cells (APCs) was sufficient for maintenance of CD8(+) T-cell numbers. However, antigen presentation by this mechanism alone yielded a memory population that displayed alterations in phenotype, cytokine production and protective capacity, indicating that antigen presentation through both hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8(+) T-cell response produced by rHuAd5. These results shed new light on the immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8(+) T-cell expansion and memory maintenance that relies upon both hematopoietic and nonhematopoietic APCs.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Bassett
authors.forename: Teng Chih
authors.initials: TC
authors.lastname: Yang
authors.forename: Dannie
authors.initials: D
authors.lastname: Bernard
authors.forename: James B
authors.initials: JB
authors.lastname: Millar
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Swift
authors.forename: A J Robert
authors.initials: AJ
authors.lastname: McGray
authors.forename: Heather
authors.initials: H
authors.lastname: VanSeggelen
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Boudreau
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Finn
authors.forename: Robin
authors.initials: R
authors.lastname: Parsons
authors.forename: Carole
authors.initials: C
authors.lastname: Evelegh
authors.forename: Daniela
authors.initials: D
authors.lastname: Damjanovic
authors.forename: Natalie
authors.initials: N
authors.lastname: Grinshtein
authors.forename: Maziar
authors.initials: M
authors.lastname: Divangahi
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wan
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Bramson
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D006413:Hematopoietic System / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines