Viral infections occur with increased frequency in patients in palliative care, impacting their quality of life and increasing mortality rates. Still, the function of the immune system has never been thoroughly studied at the end of life. We investigated virus-specific humoral and cellular immune responses in elderly end-of-life patients (n = 38) and controls (n = 28). Virus-specific T cell responses were characterized using high-parameter flow cytometry, after stimulation with cytomegalovirus (CMV) and human coronavirus OC43 peptides. Although some virus-specific T cells from patients exhibited elevated expression of costimulatory and coinhibitory molecules, their functional profile remained largely intact compared to controls. The expression of the cytotoxic markers Granzyme B, CD107a, and 2B4 on CMV-specific T cells correlated closely with survival time. Significantly, our data demonstrate that both humoral and cellular immunity remain responsive and functional against common viruses in end-of-life patients.
© 2025 The Author(s).

HIV infection significantly affects the frequencies and functions of immunoregulatory CD3+CD4-CD8- double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals during acute infection and following early ART initiation compared to 20 HIV-uninfected controls. In this study, 21 Rhesus macaques (RMs) were SIV-infected, of which 13 were assessed during acute infection and 8 following ART initiation four days post-infection. DN T-cells and FoxP3+ DN Treg frequencies increased during acute HIV infection, which was not restored by ART. The expression of activation (HLA-DR/CD38), immune checkpoints (PD-1/CTLA-4), and senescence (CD28-CD57+) markers by DN T-cells and DN Tregs increased during acute infection and was not normalized by ART. In SIV-infected RMs, DN T-cells remained unchanged despite infection or ART, whereas DN Treg frequencies increased during acute SIV infection and were not restored by ART. Finally, frequencies of CD39+ DN Tregs increased during acute HIV and SIV infections and remained elevated despite ART. Altogether, acute HIV/SIV infections significantly changed DN T-cell and DN Treg frequencies and altered their immune phenotype, while these changes were not fully normalized by early ART, suggesting persistent HIV/SIV-induced immune dysregulation despite early ART initiation.

Background: Nanofat grafting (NG) is a simple and cost-effective method of lipoaspirates with inter-syringe passages, to produce stromal vascular fraction (SVF) and isolate adipose-derived stem cells (ASCs). This represents a tremendous interest in the future clinical needs of tissue engineering. In this study, we optimized the NG technique to increase the yield of ASC extractions. Methods: We analyzed three groups of SVF obtained by 20, 30, and 40 inter-syringe passages. The control group was an SVF obtained by enzymatic digestion with Celase. We studied their cell composition by flow cytometry, observed their architecture by confocal microscopy, and observed immunomodulatory properties of the ASCs from each of the SVFs by measuring inflammatory markers of macrophages obtained by an ASC monocyte co-culture. Results: We have established the first cell mapping of the stromal vascular fraction of adipose tissue. The results showed that SVF obtained by 20 inter-syringe passages contains more statistically significant total cells, more cells expressing the ASC phenotype, more endothelial cells, and produces more CFU-F than the SVF obtained by 30 and 40 passages and by enzymatic digestion. Confocal microscopy showed the presence of residual adipocytes in SVF obtained by inter-syringe passages but not by enzymatic digestion. The functional study indicates an orientation toward a more anti-inflammatory profile and homogenization of their immunomodulatory properties. Conclusion: This study places mechanically dissociated SVF in the center of approaches to easily extract ASCs and a wide variety and number of other progenitor cells, immediately available in a clinical setting to provide both the amount and quality of cells required for decellularized tissues.
Copyright © 2022 Girard, Dulong, Duisit, Mocquard, Le Gallou, Chaput, Lupon, Watier, Varin, Tarte and Bertheuil.

CD8 T cells are key players in the clearance of human immunodeficiency virus (HIV)-infected cells, such that CD8 T-cell dysfunction contributes to viral persistence despite antiretroviral (ARV) therapy. Mesenteric lymph nodes (MLNs) are major sites of gut mucosal immunity. While different CD8 T cell subsets such as CD8 alpha-alpha (CD8αα), CD8 alpha-beta (CD8αβ), CD8 regulatory T cells (Treg), and mucosa-associated invariant T cells (MAIT) are present in the gut and exhibit distinct functions, their dynamics remain poorly understood due to the lack of accessibility to these tissues in humans. We thus assessed CD8 T cells in MLNs versus peripheral blood in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) following early ARV therapy initiation. SIV infection was associated with an increase over time of both CD8αβ and CD8αα T cells in the blood and MLNs, whereas early ARV initiation significantly decreased the frequencies of CD8αα but not CD8αβ T cells in MLNs. A significant decrease in the expression of chemokine receptors CCR6 and CXCR3 by CD8 T cells, which are essential for T-cell trafficking to the inflammatory sites, was observed in chronically SIV-infected RMs. Surprisingly, while MAIT cells are increased in ARV-treated RMs, their frequencies in MLN are extremely low and were not impacted by ARV. The acute infection resulted in an early CD39+FoxP3+ CD8 Tregs increase in both compartments, which was normalized after early ARV. Frequencies of CD8 Treg cells were positively correlated with frequencies of CD4 Tregs and accordingly negatively correlated with the Th17/Treg ratio in the blood but not in MLNs. Overall, our results underscore the difference in CD8 T-cell subset dynamics in the blood and MLNs. IMPORTANCE Changes in CD8 T-cell subsets during acute SIV/HIV infections and following early ARV initiation in gut lymphoid tissues are poorly understood. Using an acute SIV infection model in rhesus macaques, we assessed the impact of early ARV, initiated 4 days postinfection, on relative proportions of CD8 T-cell subsets in MLNs compared to blood. We found that acute SIV infection and early ARV initiation differentially affect the distribution of effector CD8 T cells, CD8 MAIT cells, and CD8 Tregs in MLNs compared to blood. Overall, early ARV initiation maintains the frequency of effector CD8 T cells while reducing immunosuppressive CD39+ CD8 Tregs. Our study provides deeper insight into the dynamics of the CD8 T-cell compartment in gut mucosal immune surveillance during acute SIV infection and following early ARV initiation.

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.