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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]

Simple Summary: Current recommendations suggest setting two parallel cytogenetic cultures with 12-O-tetradecanoly-phorpol-13-acetate (TPA) and IL2+DSP30 as a mitogen to detect complex karyotypes (CKs) in chronic lymphocytic leukemia (CLL). However, studies comparing CK detection concordance between both methods in the same cohort are lacking. Herein, we evaluated the performance of two parallel cultures in a CLL cohort of 255 patients, specifically comparing CK detection (globally and in each individual patient). The CK detection rates and their prognostic impacts were similar for both mitogens. However, nearly one-third of CKs were only identified in one culture, mainly due to the detection of a normal karyotype or no metaphases in the other. In summary, the assessment of parallel cytogenetic cultures is the best strategy to detect CKs in CLL. Nonetheless, as IL2+DSP30 achieved the best performance, it should be prioritized above TPA if a single analysis is required to optimize cytogenetic assessment in routine practice. Current CLL guidelines recommend a two parallel cultures assessment using TPA and IL2+DSP30 mitogens for complex karyotype (CK) detection. Studies comparing both mitogens for CK identification in the same cohort are lacking. We analyzed the global performance, CK detection, and concordance in the complexity assessment of two cytogenetic cultures from 255 CLL patients. IL2+DSP30 identified more altered karyotypes than TPA (50 vs. 39%, p = 0.031). Moreover, in 71% of those abnormal by both, IL2+DSP30 identified more abnormalities and/or abnormal metaphases. CK detection was similar for TPA and IL2+DSP30 (10% vs. 11%). However, 11/33 CKs (33%) were discordant, mainly due to the detection of a normal karyotype or no metaphases in the other culture. Patients requiring treatment within 12 months after sampling (active CLL) displayed significantly more CKs than those showing a stable disease (55% vs. 12%, p < 0.001). Disease status did not impact cultures' concordance (κ index: 0.735 and 0.754 for stable and active). Although CK was associated with shorter time to first treatment (TTFT) using both methods, IL2+DSP30 displayed better accuracy than TPA for predicting TTFT (C-index: 0.605 vs. 0.580, respectively). In summary, the analysis of two parallel cultures is the best option to detect CKs in CLL. Nonetheless, IL2+DSP30 could be prioritized above TPA to optimize cytogenetic assessment in clinical practice. [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]

Expansion of CD4 + CD28 null 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 + CD28 null 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 + CD28 null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4 + CD28 null 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 + CD28 null 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 + CD28 null 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 + CD28 null T-lymphocytes., (© 2024 John Wiley & Sons Ltd.)