Cellular immunology最新文献

Ibrutinib has been demonstrated to restore T cell immunity of chronic lymphocytic leukemia patients, and enhance ex vivo expansion and function of CAR-T cells. In attempt to explore the effect of ibrutinib on unmanipulated T cells, we activated human PBMCs from healthy donors with CD3/CD28 stimulation and cultured them with or without ibrutinib under various conditions. Phenotypic and functional assessments were then performed using flow cytometry. Results showed that ibrutinib could downregulate programmed cell death protein 1 expression and reduce activation-induced cell death of T cells. Additionally, ibrutinib added at the onset of T cell activation, rather than 48 h later, could further promote the generation of CD45RA⁺CCR7⁺CD95⁺ stem-cell-memory T cell subset in the presence of IL-7 and IL-15. However, ibrutinib also suppressed the proliferation and cytokine-secretion capacity of T cells in a dose-dependent manner. Further RNA sequencing of activated CD8⁺ T cells demonstrated that ibrutinib administration at the onset of T cell activation modulated multiple TCR downstream signaling pathways, notably downregulating mTORC1 signaling and upregulating FOXO1 signaling. In contrast, ibrutinib added 48 h post-activation did not show these effects. These findings suggest that caution should be exercised when incorporating ibrutinib into ex vivo expansion system for adoptive non-genetically engineered T cells or combining ibrutinib with these T cell immunotherapies in clinical trial settings.

Several vaccines targeting SARS-CoV-2 were developed following the COVID-19 outbreak. However, subsequent studies have indicated that humoral immune responses wane over time, particularly with the emergence of new SARS-CoV-2 variants. There is limited understanding of the resilience of T cell-mediated immunity induced by COVID-19 vaccines. This prospective cohort study involved a population who completed two primary doses of either the Pfizer BNT162b2 mRNA vaccine (PP) or the Sinovac Coronavac inactivated virus vaccine (SS) followed by one homologous (PPP) or heterologous (SSP) booster dose of BNT162b2, through convenience sampling of healthy adults. Blood samples were collected at three intervals, 2-weeks (T1), 6-8 months (T2), and 12-months (T3) following the booster immunization. Immunophenotyping was performed to evaluate T cell activity, memory, and intracellular cytokines at each timepoint. Our study found that the expression of T cell activation markers by both CD4+ and CD8+ T cells, such as CD25 + CD69+ and CD38 + HLA-DR+ was significantly higher at T2 compared to T1 in both PPP and SSP groups, indicating a robust T cell activation post-booster vaccination. Memory T cell subsets, including central memory and stem cell memory T cells, exhibited distinct kinetics, with both vaccines showing sustained levels of selected memory T cell subsets right up to about one year after booster. Furthermore, intracellular cytokine analysis revealed that CD4+ and CD8+ T cells in the SSP group exhibited higher level of IL-2, TNF-α and IFN-γ at specific timepoints, suggesting a stronger cellular immune response. These findings highlight the durability and qualitative differences in T cell-mediated immunity between homologous and heterologous vaccination regimens. While cellular immunity persisted in both groups up to 12 months post-booster, a decline in T3 underscores the potential, targeted need for additional booster doses to maintain protection against emerging SARS-CoV-2 variants.