In vitro proliferative responses of murine thymocytes to interleukin-1 are enhanced by supplementing the cultures with the trace nutrient zinc. Zine not only enhances the responses of cells suboptimally activated by PHA but can also prime the cells to respond to IL-1 in the absence of activation by PHA. Zinc affects the early stages of the proliferative response. The data suggest that zinc may enhance the cellular uptake of IL-1 or may facilitate enzymatic steps subsequent to IL-1 binding.
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http://dx.doi.org/10.1016/0090-1229(88)90070-0 | DOI Listing |
Front Immunol
January 2025
Integrative Immunobiology Department, Duke University, Durham, NC, United States.
Introduction: The regulation of expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage.
View Article and Find Full Text PDFDouble-strand breaks represent the most dangerous form of DNA damage, and in resting cells, these breaks are sealed via the non-homologous end joining (NHEJ) factor Ligase IV (LIG4). Excessive NHEJ may be genotoxic, necessitating multiple mechanisms to control NHEJ activity. However, a clear mechanism of transcriptional control for them has not yet been identified.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain.
Class IA PI3K p110δ and p110α subunits participate in TCR and costimulatory receptor signals involved in T cell-mediated immunity, but the role of p110α is not completely understood. Here, we analyzed a mouse model of the Cre-dependent functional inactivation of p110α (kinase dead) in T lymphocytes (p110αKD-T, KD). KD mice showed increased cellularity in thymus and spleen and altered T cell differentiation with increased number of CD4CD8 DP thymocytes, enhanced proportion of CD4 SP lymphocytes linked to altered apoptosis, lower Treg cells, and increased AKT and ERK phosphorylation in activated thymocytes.
View Article and Find Full Text PDFLeukemia
January 2025
Australian Centre for Blood Diseases (ACBD), School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-driven acquired hemolytic anemia with specific presentations of hemoglobinuria, abdominal pain, fatigue, and thrombosis.
Objective: To review the current therapeutic strategies for PNH, including anti-complement therapy and allogeneic hematopoietic cell transplantation (alloHCT), focusing on the tailoring of the approach to the disease subtype.
Results: The outcome of alloHCT varies depending on disease severity, thrombotic history, and response to prior therapies.
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