Low Double-Negative CD3+CD4-CD8- T Cells Are Associated with Incomplete Restoration of CD4+ T Cells and Higher Immune Activation in HIV-1 Immunological Non-Responders.

Xiaofan Lu,Luzia M Mayr,Xiaojie Huang,Lili Dai,Christiane Moog,Xin Zhang,Tong Zhang,Hao Wu,Yunxia Ji,Bin Su,Zixuan Yang,Huan Xia,Zhiying Liu

doi:10.3389/fimmu.2016.00579

Abstract

Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3+CD4−CD8− T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4+ T cell count. The ART did not result in complete suppression of immune activation recorded by the percentage of CD38+HLA-DR+CD8+ T cells in INRs, and a strong inverse correlation was observed between DN T cells and immune activation. A low proportion of TGF-β1+DN T cells was found in INRs. Further mechanism study demonstrated that the level of TGF-β1-producing DN T cells and immune activation had a negative correlation after ART. Taken together, our study suggests that DN T cells control the immunological response in HIV-1-infected patients. These findings expand our understanding of the mechanism of immune reconstitution and could develop specific treatments to return the immune system to homeostasis following initiation of HIV-1 therapy.

Highlights

CD3+CD4−CD8− double-negative (DN) T cells constitute approximately 1–5% of T lymphocytes in mice, non-human primates, and humans [1,2,3,4]
This study was performed to investigate the role of DN T cells in immune reconstitution of HIV-1-infected individuals
Mechanism study demonstrated that the secretion of TGF-β1 by DN T cells may be involved in the control of immune activation

Summary

Introduction

CD3+CD4−CD8− double-negative (DN) T cells constitute approximately 1–5% of T lymphocytes in mice, non-human primates, and humans [1,2,3,4]. These cells are found in the lymph nodes, lungs, and gut-associated lymphoid tissues [5,6,7,8]. The maintenance of high numbers of these DN T cells capable of secreting T helper cytokines is associated with immune activation, and it is proposed that this can contribute to the prevention of SIV disease progression in natural host monkey species [4, 5, 9]. DN T cells were identified as the latent HIV-1 reservoir that harbors HIV-1 Gag protein in the presence of antiretroviral therapy (ART) [18]

Methods

Results

Conclusion