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AIDS Res Hum Retroviruses. 2019 Mar;35(3):295-305. doi: 10.1089/AID.2018.0184. Epub 2019 Jan 2.

Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques.

Author information

1
1 Department of Microbiology, University of Washington, Seattle, Washington.
2
2 Washington National Primate Research Center, Seattle, Washington.
3
3 Profectus Biosciences, Inc., Baltimore, Maryland.

Abstract

Depletion of gut T helper 17 (Th17) cells during HIV infection leads to decreased mucosal integrity and increased disease progression. Conversely, T regulatory (Treg) cells may inhibit antiviral responses or immune activation. In HIV elite controllers, a balanced Th17/Treg ratio is maintained in the blood, suggesting a role for these responses in controlling inflammation and viral replication. HIV-infected individuals exhibit a range in responsiveness to combination antiretroviral therapy (cART). Given the link between the Th17/Treg ratio and HIV disease, we reasoned these responses may play a role in cART responsiveness. In this study, we investigated the relationship between the mucosal Th17/Treg ratio to acute simian immunodeficiency virus (SIV) viremia and the response to cART. Nineteen rhesus macaques were infected with highly pathogenic SIVΔB670 virus and cART was initiated 6 weeks postinfection. Mucosal CD4 T cell subsets were assessed by intracellular cytokine staining in the colon and mesenteric lymph nodes. Higher baseline Th17/Treg ratios corresponded with increased acute SIV viremia. Th17/Treg ratios decreased during acute SIV infection and were not restored during cART, and this corresponded to increased gut immune activation (Ki67+), markers of microbial translocation (sCD14), and T cell exhaustion (TIGIT+). Animals that maintained a more balanced mucosal Th17/Treg ratio at the time of cART initiation exhibited a better virological response to cART and maintained higher peripheral CD4 counts. These results suggest mucosal Th17 and Treg homeostasis influences acute viremia and the response to cART, a result that suggests therapeutic interventions that improve the Th17/Treg ratio before or during cART may improve treatment of HIV.

KEYWORDS:

Th17; Treg; antiretroviral therapy; mucosal immune responses; rhesus macaque; simian immunodeficiency virus

PMID:
30398361
PMCID:
PMC6434588
[Available on 2020-03-01]
DOI:
10.1089/AID.2018.0184

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