Abstract
AbstractUnlike 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.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
ANRS and the Fondation J. Beytout
U.S. Department of Health & Human Services | NIH | NIH Office of the Director
PhD fellowship from the University Paris Diderot, Sorbonne Paris Cité. ANRS and the Fondation J. Beytout
U.S. Department of Health & Human Services | NIH | National Center for Research Resources
U.S. Department of Health & Human Services | NIH | National Cancer Institute
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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