We analyzed the in vitro and in vivo effects of theophylline on various immunological parameters including proliferation of peripheral mononuclear cells (PMNC) in response to phytohemagglutinin (PHA), anti-T3 and anti-T11 monoclonal antibodies (MAb), PHA-induced interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by PMNC, interleukin-1 (IL-1) production by accessory cells, PHA-induced IL-2 production by T-cell clones, and PHA- and anti-T3 MAb-induced DNA synthesis by T cell clones. Results showed that theophylline inhibited PHA- and anti-T3-induced proliferation of both PMNC and T-cell clones, whereas the PMNC proliferation induced by MAb anti-T11 was not affected. The inhibition appeared to be dose-dependent and strictly related to the presence of the drug in the culture. Moreover, PHA-induced IL-2 production by both PMNC and T-cell clones also appeared to be reduced by theophylline. IL-1 production by accessory cells was not affected. These data suggest that the immunological inhibition exerted by theophylline is confined to the T-cell compartment, mainly by acting on structure(s) related to the T3/Ti complex, the primary site for T-cell activation. The alternative pathway of T-cell activation (i.e., via T11 site) seems unaffected. In addition, these results suggest possible clinical relations between the inhibition of the immune response and the plasma levels of the drug reached after a "once daily" or "twice daily" oral ingestion of slow-release theophylline products.
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Brief Bioinform
November 2024
Program of Cell and Gene Therapy, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil.
Antigen recognition by CD8+ T-cell receptors (TCR) is crucial for immune responses to pathogens and tumors. TCRs are cross-reactive, a single TCR can recognize multiple peptide-Human Leukocyte Antigen (HLA) complexes. The study of cross-reactivity can support the development of therapies focusing on immune modulation, such as the expansion of pre-existing T-cell clones to fight pathogens and tumors.
View Article and Find Full Text PDFAnn Clin Microbiol Antimicrob
January 2025
Marseille University Hospital Timone, Public Assistance Marseille Hospitals, Marseille Immunopole, Marseille, France.
We describe pulmonary cryptococcosis in a 28-year-old previously healthy man. Exhaustive immunological investigations revealed a primary NK cell deficiency associated with a secondary impaired anti-Cryptococcus CD8 lymphocyte response and the expansion of a CD8Vβ14 + T cell clone. This case illustrates the potential role of NK cells in immunity against Cryptococcus.
View Article and Find Full Text PDFJCI Insight
January 2025
Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America.
Thrombin promotes the proliferation and function of CD8+ T cells. To test if thrombin prevents exhaustion and sustains antiviral T cell activity during chronic viral infection, we depleted the thrombin-precursor prothrombin to 10% of normal levels in mice prior to infection with the clone 13 strain of lymphocytic choriomeningitis virus. Unexpectedly, prothrombin insufficiency resulted in 100% mortality after infection that was prevented by depletion of CD8+ T cells, suggesting that reduced availability of prothrombin enhances virus-induced immunopathology.
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January 2025
Institute for Research in Biomedicine (IRB), Bellinzona, Switzerland.
Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease characterized by the presence of autoantibodies, including those targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), also known as soluble liver antigen (SLA). Anti-SepSecS antibodies have been associated with a more severe phenotype, suggesting a key role for the SepSecS autoantigen in AIH. To analyze the immune response to SepSecS in patients with AIH at the clonal level, we combined sensitive high-throughput screening assays with the isolation of monoclonal antibodies (mAbs) and T cell clones.
View Article and Find Full Text PDFNature
January 2025
Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China.
Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers. T cells participate in a wide range of inflammatory diseases such as psoriasis, Crohn's disease, oesophagitis and multiple sclerosis, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities.
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