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Background: Memory responses to the antigens that an individual encounters throughout life may vary with the intensity and duration of antigen contacts or even with changes in immune status over time. This work aims to characterise specific responses to latent CMV, seasonal influenza and novel SARS-CoV-2 infections in immunocompetent individuals over 60 years of age. Specific cellular and humoral responses were identified by IFN-γ and granzyme B release by ELISpot and antibody level measurement. T lymphocyte subpopulation phenotypes were characterised by flow cytometry. Results: Cellular and humoral responses to these viruses were detected in almost all patients. Influenza and SARS-CoV-2 cellular responses were positively correlated. There was no significant correlation between CMV and influenza or SARS-CoV-2 responses although both were consistently lower in CMV-seropositive patients. CMV responses were negatively correlated with the levels of the least differentiated subsets of T lymphocytes, and positively correlated with the most differentiated ones, contrary to what happened with the influenza responses. Nevertheless, SARS-CoV-2 cellular responses were negatively correlated with the most differentiated CD8+ T lymphocytes, while humoral responses were negatively correlated with the least differentiated T lymphocytes. Responses to the three viruses were correlated with a Th1/Th2/Th17 balance in favour of Th1. Conclusions: The results indicate that memory responses differ depending on the durability of the antigen stimulus. Cellular responses to novel pathogens resemble those generated by seasonal but not CMV infection. Subpopulation distribution and the level of specific T lymphocytes against previous pathogens could be used as immunocompetent status biomarkers in older adults reflecting their ability to generate memory responses to new pathogens. [ABSTRACT FROM AUTHOR]

Expansion of CD4+CD28null T‐lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL‐10 is a candidate for limiting CD4+CD28null T‐lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL‐10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL‐10/TNF ratio ≥1 had significantly lower levels of CD4+CD28null T‐lymphocytes than those with a ratio <1. In vitro, IL‐10 reduced the frequency of proliferative CD4+CD28null T‐lymphocytes stimulated with anti‐CD3. Pre‐treatment with IL‐10 before anti‐CD3 stimulation was required for the cytokine to inhibit TNF production by CD4+CD28null T‐lymphocytes. In addition to the previously described effect of IL‐10 on HLA‐DR and ICAM‐1 expression, LFA‐3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL‐10 inhibition on CD4+CD28null T‐lymphocytes may be mediated by a reduction in HLA class II and LFA‐3 expression because blocking interactions with these costimulators has similar effects to those of IL‐10 treatment. Moreover, costimulation through CD2/LFA‐3 interaction is enough to induce proliferation and cytokine production in CD4+CD28null T‐lymphocytes. [ABSTRACT FROM AUTHOR]

Understanding how older people respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical if we are to confront the coronavirus disease 2019 (COVID-19) pandemic and establish effective vaccination strategies. Immunosenescence reduces the ability to respond to neoantigens and may compromise the life of infected individuals. Here, we analyzed the immunological memory to SARS-CoV-2 in 102 recovered patients aged over 60 years several months after the infection had been resolved. Specific memory T lymphocytes against the virus were measured by interferon-γ (IFN-γ) and granzyme B release by ELISpot; memory B-lymphocyte responses were quantified by detection of anti-S IgG1 producer cells by ELISpot and anti-S and anti-N antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than 7 months after the infection in some of them. Fewer patients maintained memory B lymphocytes, but antibodies, mainly anti-S, were highly durable and positively correlated with T responses. More robust humoral responses were found in patients who had more severe symptoms and had been admitted to hospital. We concluded that specific immunity against SARS-CoV-2 is effectively preserved regardless of age, despite the great heterogeneity of their immune responses, and that memory T lymphocytes and anti-S IgG might be more durable than memory B cells and anti-N IgG. [ABSTRACT FROM AUTHOR]

Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC). High differentiation of CD8+ T-lymphocytes was found in CMV-seropositive patients; however, the differentiation of CD4+ T-lymphocytes was increased in CMV-seropositive but also in CHF patients. Anti-CMV antibody titers showed positive correlation with more differentiated CD4+ and CD8+ subsets and inverse correlation with CD4/CD8 ratio. Immunosenescence found in CHF patients is mainly due to the dynamics of CMV-infection, since the differentiation of T-lymphocyte subsets is related not only to CMV-infection, but also to anti-CMV antibody titers. [ABSTRACT FROM AUTHOR]

Expanded CD4+CD28null T lymphocytes are found in the tissues and peripheral blood of patients with many autoimmune diseases, such as rheumatoid arthritis (RA). These highly differentiated cells present potent inflammatory activity and capability to induce tissue destruction, which has been suggested to predispose to the development of more aggressive disease. In fact, preferential migration to inflammatory sites has been proposed to be a contributing factor in the progression of autoimmune and cardiovascular diseases frequently found in these patients. The functional activity of CD4+CD28null T lymphocytes is largely dependent on interleukin 15 (IL-15), and this cytokine may also act as a selective attractor of these cells to local inflammatory infiltrates in damaged tissues. We have analysed, in RA patients, the migratory properties and transcriptional motility profile of CD4+CD28null T lymphocytes compared to their counterparts CD28+ T lymphocytes and the enhancing role of IL-15. Identification of the pathways involved in this process will allow us to design strategies directed to block effector functions that CD4+CD28null T lymphocytes have in the target tissue, which may represent therapeutic approaches in this immune disorder. [ABSTRACT FROM AUTHOR]