IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques.
Justin L HarperNicolas HuotLuca MicciGregory K TharpColin KingPhilippe RascleNeeta ShenviHong WangCristin GalardiAmit A UpadhyayFrancois VillingerJeffrey LifsonGuido SilvestriKirk A EasleyBeatrice JacquelinSteven E BosingerMichaela Müller-TrutwinMirko PaiardiniPublished in: Nature communications (2021)
Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy, nonpathogenic infections in natural hosts, such African green monkeys, are characterized by a lack of gut microbial translocation and robust secondary lymphoid natural killer cell responses resulting in an absence of chronic inflammation and limited SIV dissemination in lymph node B-cell follicles. Here we report, using the pathogenic model of antiretroviral therapy-treated, SIV-infected rhesus macaques that sequential interleukin-21 and interferon alpha therapy generate terminally differentiated blood natural killer cells (NKG2a/clowCD16+) with potent human leukocyte antigen-E-restricted activity in response to SIV envelope peptides. This is in contrast to control macaques, where less differentiated, interferon gamma-producing natural killer cells predominate. The frequency and activity of terminally differentiated NKG2a/clowCD16+ natural killer cells correlates with a reduction of replication-competent SIV in lymph node during antiretroviral therapy and time to viral rebound following analytical treatment interruption. These data demonstrate that African green monkey-like natural killer cell differentiation profiles can be rescued in rhesus macaques to promote viral clearance in tissues.
Keyphrases
- natural killer cells
- antiretroviral therapy
- lymph node
- hiv infected
- nk cells
- human immunodeficiency virus
- hiv infected patients
- hiv aids
- hiv positive
- dendritic cells
- sars cov
- neoadjuvant chemotherapy
- gene expression
- cell therapy
- magnetic resonance
- mouse model
- radiation therapy
- magnetic resonance imaging
- stem cells
- oxidative stress
- single cell
- big data
- anti inflammatory
- mass spectrometry
- hepatitis c virus
- men who have sex with men
- amino acid
- smoking cessation