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IL-21 Therapy Controls Immune Activation and Maintains Antiviral CD8+ T Cell Responses in Acute Simian Immunodeficiency Virus Infection.

Abstract：

:Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replicate during acute infection in lymphocytes of the gastrointestinal tract, before disseminating systemically. Localized replication and associated loss of gut-resident CD4+ T cells occur regardless of the portal of entry of the virus (e.g., intravenous vs. rectal). Thus, HIV and SIV are tropic for gut tissue, and their pathogenesis requires the special environment of the intestine. T helper 17 (Th17) cells are important contributors to microbial defense in the gut that are vulnerable to HIV infection and whose loss is associated with translocation of microbial products to the systemic circulation, leading to chronic immune activation and disease progression. Interleukin (IL)-21 promotes differentiation and survival of Th17 cells and stimulates CD8+ T cell function. By promoting Th17 cell survival, IL-21 could limit bacterial translocation and immune activation in the setting of acute or rebounding HIV/SIV disease. In this study, we tested the effect of recombinant IL-21-IgFc treatment, given at the time of infection, on SIVmac251 infection. We found that rIL-21-IgFc decreases immune activation and maintains effective antiviral responses by CD8+ T cells in blood, but this maintenance is not associated with lower viral loads. rIL-21-IgFc treatment also did not generally support Th17 cell populations, but Th17 cells remained strongly and independently associated with control of plasma viremia. For example, the single animal exhibiting greatest control over viremia in our study also manifested the highest levels of IL-21 in plasma, Th17 cell maintenance in blood, and Th17 cells in intestinal tissue. These findings provide rationale for further exploration of IL-21 treatment as a support for host CD8+ T cell responses in HIV cure strategies.

journal_name

AIDS Res Hum Retroviruses

journal_title

AIDS research and human retroviruses

authors

Méndez-Lagares G,Lu D,Merriam D,Baker CA,Villinger F,Van Rompay KKA,McCune JM,Hartigan-O'Connor DJ

doi

10.1089/aid.2017.0160

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

S81-S92

issue

eissn

0889-2229

issn

1931-8405

journal_volume

pub_type

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IL-21 Therapy Controls Immune Activation and Maintains Antiviral CD8+ T Cell Responses in Acute Simian Immunodeficiency Virus Infection.