Altered T-Cell Subsets are Associated with Dysregulated Cytokine Secretion of CD4+ T Cells During HIV Infection

Abstract

Background: CD4 + T cells play a critical role in the regulation of immunopathogenesis in HIV infection. Previous studies have shown contradictory results of the CD4 + T-cell responses in people living with HIV (PLHIV). Methods: A cross-sectional study was performed on 40 healthy controls, 134 ART-naïve PLHIV, and 34 individuals who experienced 3-year ART with low baseline CD4 count from 4 August 2016 to 23 January 2019. We determined the frequencies of CD4 + T-cell subsets and described the cytokine secretion pattern of total and subsets of CD4 + T cells in these individuals. Results: We found that CD4 + T cells in PLHIV displayed enhanced secretion of proinflammation cytokines and polyfunctionality due to HIV disease progression (r = −0.282, P = 0.0035 for IFN-γ; r = −0.412, P = 0.0002 for TNF-α; r = −0.243, P < 0.0001 for GM-CSF; r = −0.252, P = 0.0093 for IFN-γ + TNF-α + cells). However, the altered T-cell subsets, as presented by the loss of naïve cells and expansion of memory/effector population in PLHIV, were associated with discordant results in total and subsets of CD4 + T cells. As major cytokine-producing T subsets, effector/memory CD4 subsets showed impaired cytokine production (P < 0.05). We further demonstrated that 3-year ART treatment could improve CD4 counts by increasing the pool of naïve T cells but could not restore cytokine secretion in CD4 + T-cell subsets (P < 0.05). Conclusion: These data identified the impaired capacity of cytokine secretion in CD4 + T-cell subsets due to HIV disease progression, and the altered T-cell subsets were associated with pseudo-elevation of cytokine production in total CD4 + T cells. This study collectively suggested the importance of therapies that can preserve and/or enhance the function of CD4 + T cells in strategies of HIV remission.

Clinical Association of Viral Tropism and Serum Cytokines in Untreated HIV-1 Infection Patients

“…HIV-1 entry into cells is mediated by Env consisting of two subunits, gp120 and gp41. The initial interaction occurs between HIV-1 and host cell mediated by combination of gp120 and the cell surface receptor CD4 [3,4,6]. Subsequently, structural gp120 rearrangements emerge, which causes exposure of the coreceptor binding sites and secondary combination of CCR5 or CXCR4 chemokine receptor [11].…”

“…Human immunode ciency virus type 1 (HIV-1) infection is characterized by the immune cell destruction and immune system hyperactivation, which ultimately causes death in AIDS patients [1]. At the acute stage of infection, a rapid replication of HIV-1 and a simultaneous decrease of CD4 + T cells accompany with the release of various cytokines [2] Cytokines as the effectors and modi ers of in ammation produced by innate and adaptive immune cells are responsible for intercellular immune regulation and communication [3][4][5]. According to their lineages, different immune cells, including macrophages, Th1, Th2, and Th17 cells, can secrete IL-1β, IL-2, IL-4, IL-10, IL-17, IFNs, TNF-α, and GM-CSF [6].…”

The roles of Th cells in myocardial infarction

“…The administration of recombinant IL-22 showed a protective effect against HIV-induced intestinal epithelial damage. Therefore, the study’s findings suggest that the reduction of IL-22 secretion and Th22 depletion in the intestinal mucosa play a significant role in the pathogenesis of HIV mucosal immunity [ 143 ]. In hepatitis B virus (HBV) infected individuals, IL-22 can activate the production of liver stem/progenitor cells (LPC) by activating the STAT3 pathway, achieving a protective role in HBV infection [ 144 ].…”