title: Extralymphoid CD8+ T cells resident in tissue from simian immunodeficiency virus SIVmac239{Delta}nef-vaccinated macaques suppress SIVmac239 replication ex vivo.
abstract: Live-attenuated vaccination with simian immunodeficiency virus (SIV) SIVmac239Deltanef is the most successful vaccine product tested to date in macaques. However, the mechanisms that explain the efficacy of this vaccine remain largely unknown. We utilized an ex vivo viral suppression assay to assess the quality of the immune response in SIVmac239Deltanef-immunized animals. Using major histocompatibility complex-matched Mauritian cynomolgus macaques, we did not detect SIV-specific functional immune responses in the blood by gamma interferon (IFN-gamma) enzyme-linked immunospot assay at select time points; however, we found that lung CD8(+) T cells, unlike blood CD8(+) T cells, effectively suppress virus replication by up to 80%. These results suggest that SIVmac239Deltanef may be an effective vaccine because it elicits functional immunity at mucosal sites. Moreover, these results underscore the limitations of relying on immunological measurements from peripheral blood lymphocytes in studies of protective immunity to HIV/SIV.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 585 Science Drive, Madison, WI 53711, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Lhost
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Melisa L
authors.initials: ML
authors.lastname: Budde
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Macnair
authors.forename: Madelyn K
authors.initials: MK
authors.lastname: Weiker
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015754:Genes, nef; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D008252:Macaca fascicularis; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014779:Virus Replication
chemical_list: D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D007371:Interferon-gamma