Background And Aim Of The Study: Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease (RHD). The CD4+CD25+ T cell (Tregs) is the chief regulator of autoimmunity, and is essential for the induction and maintenance of self-tolerance and prevention of autoimmunity. To date, the levels of Tregs in RHD have not been investigated. Hence, the study aim was to monitor levels of circulating Tregs in patients with RHD, and to determine whether these differ according to the extent of valvular involvement.
Methods: A total of 100 adult patients with RHD and 50 age- and gender-matched controls were studied. Patients were subdivided according to the extent of left-sided valvular involvement. Those with echocardiographic evidence only of significant mitral valve disease were enrolled in the univalvular group, while those with significant involvement of both mitral and aortic valves were allocated to the multivalvular group. Levels of circulating Tregs were determined using flow cytometry.
Results: Levels of Tregs in total lymphocytes and CD4+ T lymphocytes were significantly lower in RHD patients than in controls (3.55 +/- 2.28% versus 5.76 +/- 4.2%; p < 0.001, and 14.4 +/- 9.4% versus 18.6 +/- 10.4%; p = 0.011, respectively). Within the study group, the proportion of Tregs to total and CD4+ T lymphocytes was significantly lower in patients with multivalvular than with univalvular disease (2.7 +/- 1.52% versus 4.41 +/- 2.58%; p = 0.001 and 11.5 +/- 8.5% versus 17.4 +/- 9.4%; p = 0.001, respectively).
Conclusion: The present study was the first to demonstrate a significant deficiency of circulating Tregs in RHD patients; notably, the reduction was greater in patients with multivalvular than with univalvular involvement.
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J Immunother Cancer
January 2025
Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
Purpose: Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.
Experimental Design: In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.
iScience
December 2024
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs).
View Article and Find Full Text PDFMed
December 2024
Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK. Electronic address:
Background: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase 1 clinical trial of Treg therapy in living donor renal transplantation, the ONE Study (ClinicalTrials.gov: NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression.
View Article and Find Full Text PDFJ Neuroinflammation
December 2024
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Background: The global incidence of type 2 diabetes (T2D) is rapidly increasing, with retinopathy being its most common complication and a leading cause of preventable blindness. Although the precise mechanisms involved in the development of diabetic retinopathy (DR) are not fully understood, defective immunomodulation is a recognized key factor in its pathophysiology. Regulatory T cells (Treg) regulate inflammation and promote regeneration, and while they are known to have important anti-inflammatory and neuroprotective roles in other tissues, including central nervous system, their role in the diabetic retina remains largely unknown.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK; NIHR, Biomedical Research Centre, Newcastle Upon Tyne, UK. Electronic address:
Regulatory T cells (Tregs) are immune regulatory T cells that are vital for controlling inflammation. The role of Tregs in inflammatory diseases namely psoriatic arthritis (PsA) is still poorly understood. The underlying reason being a lack of robust unbiased analysis to test the immune regulatory phenotype of human Tregs.
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