Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV-specific CD4+T-cell-dependent natural killer cell effector responses in chronically infected rhesus macaques

AbstractTfh initiates four eradicable immunities. Tfh includes FDC, LTi, IL21 CD4 T cell, and IgG/M B cell. Treg initiates four tolerable immunities. Treg includes DCreg, ILCreg, TGFβ CD4 T cell, and IgA B cell. TH1/TH1-like is immunity for intracellular bacteria/protozoa and type 4 delayed type hypersensitivity. TH1 includes M1 macrophage, mDC2, Tc1 CD8 T cell, IFNg CD4 T cell, ILC1, iNKT1, and IgG3 B cell. TH1-like includes M2 macrophage, ILC1, suppressive CD8 T cell, IFNg/TGFβ CD4 T cell, regulatory iNKT cells, and IgA1 B cell. TH2/TH9 is immunity for helminths and type1 IgE mediated hypersensitivity. TH2 includes iEOS eosinophil, Langerhans cell, basophil/MCt mast cell, IL-4 CD4 T cell, ILC2, iNKT2, and IgE/IgG4 B cell. TH9 includes rEOS eosinophil, basophils/mast cell MCct, IL-9 CD4 T cell, ILC2, regulatory iNKT cells, and IgA2 B cell. TH22/TH17 is immunity for extracellular bacteria/fungi and type 3 immune complex hypersensitivity. TH22 includes N1 neutrophils, mDC1, IL-22 CD4 T cell, ILC3(NCR+), iNKT17, and IgG2 B cell. TH17 includes N2 neutrophils, IL-17 CD4 T cell, regulatory iNKT cells, ILC3(NCR−), and IgA2 B cell. THαβ/TH3 is immunity for viruses and type 2 antibody dependent cytotoxic hypersensitivity. THαβ includes NK1 natural killer cell, pDC, Tc2 CD8 T cell, IL10 CD4 T cell, ILC10, iNKT10, and IgG1 B cell. TH3 includes NK2 natural killer cell, suppressive CD8 T cell, ILC10, IL-10/TGFβ CD4 T cell, regulatory iNKT cells, and IgA1 B cell.Summary sentenceThe summarized framework of host immunities to explain their relations to specific pathogens and hypersensitivities

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IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques

Nature Communications ◽

10.1038/s41467-021-23189-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Justin Harper ◽

Nicolas Huot ◽

Luca Micci ◽

Gregory Tharp ◽

Colin King ◽

...

Keyword(s):

Lymph Node ◽

Antiretroviral Therapy ◽

Natural Killer Cells ◽

Natural Killer Cell ◽

Natural Killer ◽

Rhesus Macaques ◽

Killer Cell ◽

Human Leukocyte ◽

Analytical Treatment ◽

Killer Cells

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.

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