Isabel María Vallejo-Bermúdez

CD57-expressing lymphocytes constitute a distinct subset of immune cells with enhanced cytotoxic and pro-inflammatory functions. Initially described in the context of chronic viral infections, most notably cytomegalovirus (CMV), these cells are now recognized as central contributors to immunosenescence and age-related immune dysregulation. Their progressive accumulation reflects prolonged antigenic exposure and sustained immune activation, thereby linking persistent viral infections with long-term disruptions of immune homeostasis. Emerging evidence indicates that CD57 expression denotes a state of terminal differentiation in both T and natural killer (NK) cell compartments, and is associated with cytotoxicity, altered cytokine secretion, and a pro-inflammatory phenotype. This review summarizes the phenotypic and functional characteristics of CD57⁺ lymphocytes, examines their association with CMV and other chronic viral infections, and explores their potential role in ageing and age-related diseases. Elucidating the biology of CD57⁺ lymphocytes in the context of chronic viral infections may provide novel insights into immune ageing and help identify potential targets for therapeutic strategies aimed at restoring immune balance in older adults.

Background: Annual influenza vaccine updates target viral drift, but immune responses may be biased by original antigenic sin (OAS). Few studies have explored this across closely related strains. This study examines how OAS shapes responses to sequential influenza variants in the context of seasonal vaccination. Methods: We conducted a prospective, longitudinal study to assess the humoral immune response to the 2023–2024 seasonal influenza vaccine containing the A/Victoria/4897/2022 (H1N1) strain. Bioinformatic analyses compared the hemagglutinin (HA) sequences of A/Victoria/4897/2022 and the antigenically related A/Victoria/2570/2019 strain. B-cell epitopes were mapped with BepiPred-3.0 and BepiBlast, and their physicochemical properties analyzed via accessibility, β-turns, flexibility, and hydrophilicity. Antibody responses were measured pre- and 28 days post-Vaxigrip Tetra vaccination in young (18–35) and older (>65) adults, stratified by cytomegalovirus (CMV) serostatus. HA sequences showed >97% identity, with variations mainly in the globular head. Predicted B-cell epitopes overlapped variable sites, suggesting possible immune escape. Despite having been vaccinated against the 2022 strain, serology showed higher antibody titers against the 2019 HA strain in all participants. This pattern suggests a potential antigen imprinting effect, though confirmation awaits further analysis. Age groups differed: older adults showed greater variability, while younger CMV+ individuals tended toward stronger 2019 HA responses. Conclusions: These findings suggest a complex interplay of factors shaping immune responses, though the imprinting effect and the potential role of CMV warrant further exploration in larger, more focused studies.

Coronary artery disease (CAD) remains a major cause of cardiovascular morbidity and mortality, with growing evidence linking immune dysregulation to its pathogenesis. Aortic stenosis often coexists with CAD (ASCAD), representing an advanced disease form. This study investigates immune pathways in isolated CAD (iCAD) and ASCAD. For this purpose, peripheral blood from 72 individuals (healthy donors, iCAD, and ASCAD patients) was analysed via flow cytometry to assess immune populations. Circulating cytokine levels were measured, and machine learning models identified predictive immune biomarkers. Our data showed that both iCAD and ASCAD patients exhibited immune dysregulation, with reduced dendritic cells, basophils, NK cells, B cells, and T cells, alongside lower frequencies of DCs, lymphocytes, CD8+CD28+ T cells, and CD57+ T cells. Elevated IL-15 and fractalkine, but reduced IL-8 and MCP-1, suggest impaired monocyte and neutrophil mobilisation due to immune cell sequestration in vascular lesions. Distinct immune features emerged between iCAD and ASCAD. iCAD patients showed heightened immune activation, with increased inflammatory CD14+CD16+ monocytes, higher Treg frequencies, and greater CD4+ T cell differentiation into TEM and TEMRA phenotypes. In contrast, ASCAD patients exhibited pronounced immunosenescence, with higher neutrophil counts, lymphopenia, and increased NK and T cell cytotoxicity. Our predictive model distinguished iCAD from ASCAD with high accuracy, identifying CD4+ T cell memory subsets and CD57 expression as key discriminators. This study reveals iCAD as being driven by immune activation and ASCAD by immunosenescence and cytotoxicity. These insights advance CAD immunopathology understanding and support immune-based classification, particularly for ASCAD, where treatment remains limited to surgical intervention.