Natural killer cell phenotype is altered in HIV-exposed seronegative women

Abstract

Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls. We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4 + T cells, we observed that NKp30 + and Siglec-7 + cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with larger cohorts are warranted to confirm these findings.

Natural Killer Cells in Immunotherapy: Are We Nearly There?

“…HESN NK cells present increased expression of NKG2A, NKp30, LILRB1, and CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. These NK cells have increased ADCC, which correlates with increased CD16 [99].…”

HIV-Exposed Seronegative Sex Workers Express Low T-Cell Activation and an Intact Ectocervical Tissue Microenvironment

“…Such high-risk subjects are referred to as HIV-exposed seronegative (HESN) individuals and include sex workers, HIV-status discordant couples, intravenous drug users, and children born to untreated HIV-infected mothers. Relative resistance to HIV infection is likely multi-factorial and several studies have identified innate immune and anti-inflammatory factors, HIV-specific T- and B-cell responses, increased regulatory T- and B-cell activity as well as genetic and epigenetic correlates to this phenotype [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

The Importance of Regulation in Natural Immunity to HIV

“…TIGIT expression by memory T-cells correlated with HIV disease progression, with T-cells from elite controllers expressing lower levels of TIGIT than viremic individuals or even ART-treated individuals [ 171 ], and a blockage of TIGIT expression by NK cells increased their anti-tumoral cytotoxicity by preventing cell exhaustion [ 170 ]. In Beninese HESN women, a slightly higher expression of TIGIT was found when compared to healthy donors [ 172 ]. As to whether this slight increase of TIGIT correlates with a gain of function remains to be established.…”

“…Studies conducted with the Beninese CSWs cohort showed that while NK cells of HESN women did not cluster into a different subset when compared to uninfected women, they expressed higher levels of CD16 (FCɣRIII) [ 172 ]. CD16 is an Fc receptor that allows binding to IgG Fc portion, and whose binding is essential to ADCC activity by NK cells [ 165 ].…”