title: Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination.
abstract: Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Jamal
authors.initials: J
authors.lastname: Baig
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Levy
authors.forename: Paul F
authors.initials: PF
authors.lastname: McKay
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.forename: Ramu A
authors.initials: RA
authors.lastname: Subbramanian
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lifton
authors.forename: Darci A
authors.initials: DA
authors.lastname: Gorgone
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Chakrabarti
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D003106:Colon / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D007583:Jejunum / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA