Thymosin α1-induced secretion of the IL-15/RA complex by THP-1-derived dendritic cells restrains HIV latency in vitro.
Thymosin α1 stimulation in vitro enhances immune responses in CD8+ T cells and reduces HIV reservoir size, but these findings need further investigation in clinical settings.
Where it sits
this study against the rest of the thymosin alpha-1 corpusSummary and findings
This study investigated the effects of Thymosin α1 (Tα1) on immune responses in peripheral blood mononuclear cells (PBMCs) from people living with HIV-1. Tα1 stimulation of mature dendritic cells led to significant immune responses, including increased secretion of the IL-15/RA complex and enhanced CD8+ T cell functionality. The study did not report any therapeutic claims.
Abstract
Viral reservoir presents a significant challenge in HIV-1 cure. We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway. However, the precise mechanism remains to be fully elucidated. Peripheral blood mononuclear cells (PBMCs) were obtained from people living with HIV-1 (PLWH). In vitro, THP-1 cells were differentiated into mature monocyte-derived dendritic cells (MoDCs) and co-cultured with PBMCs under various conditions. Intracellular HIV-1 p24 levels, CD8+ T and NK cell functionality, and reservoir size were evaluated. In vitro, Tα1 stimulation of MoDCs resulted in significant immune response and secretion of IL-15/RA complex (<i>p</i> < 0.001). This interaction with IL-2 Rβ/γ receptors on T cells enhanced the intracellular secretion of CCL3/5, IFN-γ, and TNF-α in CD8+ T cells (<i>p</i> < 0.05), which inhibited p24 levels in CD4+ T cells (<i>p</i> = 0.002), and reduced HIV-1 integrated DNA levels (<i>p</i> = 0.012). Furthermore, the secretion levels of IFN-γ, TNF-α, and GZMB in NK cells and proportion of CD8+ T<sub>VM</sub> cells significantly increased following co-culture. These alterations were found to be markedly inversely associated with reservoir size and reactivation. However, these effects were observed in PBMCs from immunological responders (CD4+ T cell count > 350 cells/µL) rather than nonresponders. Tα1 enhances CD8+ T cell function, promotes T<sub>VM</sub> proliferation, and suppresses reservoir size and reactivation via IL-15 pathway activation in dendritic cells, which warrants testing in functional cure trials in the future.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.