ABSTRACT
The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/ß-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/ß-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/ß-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Precursor Cells, T-Lymphoid/immunology , Wnt Signaling Pathway/immunology , Aging/immunology , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Gene Expression Profiling , HIV Infections/immunology , Humans , Immunologic Memory , Intercellular Signaling Peptides and Proteins/metabolism , Mice , Thymus Gland/immunology , Wnt Signaling Pathway/genetics , beta Catenin/immunologyABSTRACT
BACKGROUND: This study introduces a newly Chinese domestic-designed/manufactured bovine pericardial valve, the SCBC valve (Shanghai Cingular Biotech Corporation, Shanghai, China), and evaluates its hemodynamic performance and calcification potential compared with the Carpentier-Edwards (CE) Perimount(TM) valve (Edwards Lifesciences, Irvine, CA, USA) in juvenile sheep for preclinical study. METHODS: Five SCBC valves in study group and three CE Perimount(TM) valves (6900P with TFX) in control group were implanted in the mitral position of juvenile sheep and followed up for five months. Transthoracic echocardiography (TTE) for hemodynamic measurement was performed ten days, three months and five months postoperatively. Valve calcification was assessed by X-ray after euthanasia. Other collected data included macroscopic examination, blood analysis, microorganism culture and histological assessment. RESULTS: All sheep in two groups lived to sacrifice without evidence of valvular dysfunction. The SCBC valve had similar hemodynamic performance and susceptibility of calcification compared with the CE Perimount(TM) valve in juvenile ovine model. In all other parameters, the SCBC valve also exhibited no significant difference compared with the CE Perimount(TM) valve. CONCLUSIONS: Our study demonstrated that the SCBC valve can exhibit similar mid-term satisfactory safety and efficacy compared with the CE Perimount(TM) valve in the mitral position of juvenile sheep model.
ABSTRACT
BACKGROUND: Chikungunya virus (CHIKV) infection induces arthralgia. The involvement of inflammatory cytokines and chemokines has been suggested, but very little is known about their secretion profile in CHIKV-infected patients. METHODS: A case-control longitudinal study was performed that involved 30 adult patients with laboratory-confirmed Chikungunya fever. Their profiles of clinical disease, viral load, and immune mediators were investigated. RESULTS: When patients were segregated into high viral load and low viral load groups during the acute phase, those with high viremia had lymphopenia, lower levels of monocytes, neutrophilia, and signs of inflammation. The high viral load group was also characterized by a higher production of pro-inflammatory cytokines, such as interferon-α and interleukin (IL)-6, during the acute phase. As the disease progressed to the chronic phase, IL-17 became detectable. However, persistent arthralgia was associated with higher levels of IL-6 and granulocyte macrophage colony-stimulating factor, whereas patients who recovered fully had high levels of Eotaxin and hepatocyte growth factor. CONCLUSIONS: The level of CHIKV viremia during the acute phase determined specific patterns of pro-inflammatory cytokines, which were associated with disease severity. At the chronic phase, levels of IL-6, and granulocyte macrophage colony-stimulating factor found to be associated with persistent arthralgia provide a possible explanation for the etiology of arthralgia that plagues numerous CHIKV-infected patients.
