IL-21 Expands HIV-1-Specific CD8 T Memory Stem Cells to Suppress HIV-1 Replication In Vitro

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2019 Jun 12

PMID 31183385

Citations 4

Authors

Kang Wu

Shaoying Zhang

Xu Zhang

Xinghua Li

Zhongsi Hong

Fei Yu

Bingfeng Liu

Ting Pan

Zhaofeng Huang

Xiao-Ping Tang

Weiping Cai

Jinyu Xia

Xuefeng Li

Hui Zhang

Yiwen Zhang

Linghua Li

Affiliations

Soon will be listed here.

Abstract

Due to the existence of viral reservoirs, the rebound of human immunodeficiency virus type 1 (HIV-1) viremia can occur within weeks after discontinuing combined antiretroviral therapy. Immunotherapy could potentially be applied to eradicate reactivated HIV-1 in latently infected CD4 T lymphocytes. Although the existence of HIV-1-specific CD8 T memory stem cells (Ts) is well established, there are currently no reports regarding methods using CD8 Ts to treat HIV-1 infection. In this study, we quantified peripheral blood antigen-specific CD8 Ts and then expanded HIV-1-specific Ts that targeted optimal antigen epitopes (SL9, IL9, and TL9) in the presence of interleukin- (IL-) 21 or IL-15. The suppressive capacity of the expanded CD8 Ts on HIV-1 production was measured by assessing cell-associated viral RNA and performing viral outgrowth assays. We found that the number of unmutated TL9-specific CD8 Ts positively correlated with the abundance of CD4 T cells and that the expression of IFN- was higher in TL9-specific CD8 Ts than that in non-TL9-specific CD8 Ts. Moreover, the antiviral capacities of IL-21-stimulated CD8 Ts exceeded those of conventional CD8 memory T cells and IL-15-stimulated CD8 Ts. Thus, we demonstrated that IL-21 could efficiently expand HIV-1-specific CD8 Ts to suppress HIV-1 replication. Our study provides new insight into the function of IL-21 in the suppression of HIV-1 replication.

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