NK Cell Responses to SIV Vaginal Exposure in Naïve and Vaccinated Rhesus Macaques1

• Published in: The Journal of immunology (1950) Vol. 193; no. 1; pp. 277 - 284
• Main Authors: Shang, Liang, Smith, Anthony J, Duan, Lijie, Perkey, Katherine E., Qu, Lucy, Wietgrefe, Stephen, Zupancic, Mary, Southern, Peter J., Masek-Hammerman, Katherine, Reeves, R. Keith, Johnson, R. Paul, Haase, Ashley T
• Format: Journal Article
• Language: English
• Published: 04.06.2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1400417

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. Here 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 one week, and was thus 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 rapidly decreased in the second week, in an inverse relationship to the peak of local SIV RNA + cells. 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/IL2Rβ. 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.