title: NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.
abstract: NK cell responses to HIV/SIV infection have been well studied in acute and chronic infected patients/monkeys, but little is known about NK cells during viral transmission, particularly in mucosal tissues. In this article, we report a systematic study of NK cell responses to high-dose vaginal exposure to SIVmac251 in the rhesus macaque female reproductive tract (FRT). Small numbers of NK cells were recruited into the FRT mucosa following vaginal inoculation. The influx of mucosal NK cells preceded local virus replication and peaked at 1 wk and, thus, was in an appropriate time frame to control an expanding population of infected cells at the portal of entry. However, NK cells were greatly outnumbered by recruited target cells that fuel local virus expansion and were spatially dissociated from SIV RNA+ cells at the major site of expansion of infected founder populations in the transition zone and adjoining endocervix. The number of NK cells in the FRT mucosa decreased rapidly in the second week, while the number of SIV RNA+ cells in the FRT reached its peak. Mucosal NK cells produced IFN-γ and MIP-1α/CCL3 but lacked several markers of activation and cytotoxicity, and this was correlated with inoculum-induced upregulation of the inhibitory ligand HLA-E and downregulation of the activating receptor CD122/IL-2Rβ. Examination of SIVΔnef-vaccinated monkeys suggested that recruitment of NK cells to the genital mucosa was not involved in vaccine-induced protection from vaginal challenge. In summary, our results suggest that NK cells play, at most, a limited role in defenses in the FRT against vaginal challenge.
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Liang
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Perkey
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Lucy
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wietgrefe
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Mary
authors.initials: M
authors.lastname: Zupancic
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Southern
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772.
authors.forename: Katherine
authors.initials: K
authors.lastname: Masek-Hammerman
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; and haase001@umn.edu.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D018928:Immunity, Mucosal; D007694:Killer Cells, Natural / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014621:Vagina / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines