Purpose: Apoptosis of circulating CD8+ T cells seen in patients with squamous cell carcinoma of the head and neck [SCCHN (Hoffmann T, et al. Clin Cancer Res 2002;8:2553-62)] suggested a possibility of lymphocyte imbalance. Therefore, absolute numbers and percentages of lymphocyte subsets were examined in the peripheral blood of SCCHN patients and controls.
Experimental Design: Venous blood was obtained from 146 patients with SCCHN and 54 normal volunteers. Absolute numbers of CD3+, CD4+, and CD8+ T lymphocytes were determined using fluorobeads in a flow cytometry-based technique. Percentages of T lymphocyte subsets were also evaluated by flow cytometry. The patients were grouped at the time of blood draw [active versus no evidence of disease (NED), type of therapy administered, and the length of follow-up].
Results: Patients with SCCHN had significantly lower absolute numbers of CD3+ CD4+, and CD8+ T cells than normal controls. However, no differences in the percentages of T-cell subsets between patients and normal controls were observed. Patients with active disease had significantly lower CD3+ and CD4+ T-cell counts than those with NED. Patients who had NED after surgery and radiotherapy had the lowest T-cell counts among the NED cohort. Patients who had NED for >2 years did not recover their T-cell counts, and the T-cell imbalance was evident many years after curative surgery. The tumor-node-metastasis (TNM) stage or site of the disease was not related to the absolute T-cell count. Patients with recurrent disease at the time of blood draw tended to have the lowest CD4+ T-cell counts.
Conclusions: Patients with SCCHN have altered lymphocyte homeostasis, which persists for months or years after curative therapies.
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http://dx.doi.org/10.1158/1078-0432.CCR-04-0054 | DOI Listing |
Inflamm Res
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Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
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Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.
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School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
Introduction: SLE is a chronic autoimmune disease that results in sustained hyperactivation of innate and adaptive immune cells and widespread inflammatory damage. Regular exercise reduces SLE symptoms including fatigue and joint pain and improves patient quality of life. However, most individuals with SLE are not sufficiently active to achieve these benefits, and guidance on the optimal approach to exercise is limited.
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Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
The management of autoimmune diseases is currently limited by therapies that largely suppress the immune system, often resulting in partial and temporary remissions. Cellular immunotherapies offer a targeted approach by redirecting immune cells to correct the underlying autoimmunity. This review explores the latest advances in cellular immunotherapies for autoimmune diseases, focusing on various strategies, such as the use of chimeric antigen receptor (CAR) T cells, chimeric auto-antibody receptor (CAAR) T cells, regulatory T cells (Tregs), and tolerogenic dendritic cells (TolDCs).
View Article and Find Full Text PDFPLoS One
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Bioscience COPD/IPF, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Multiple genetic associations suggest a causative relationship between Th17-related genes coding for proteins, such as IL-17A, IL-23 and STAT3, and psoriasis. Further support for this link comes from the findings that neutralizing antibodies directed against IL-17A, IL-17RA and IL-23 are efficacious in diseases like psoriasis, psoriatic arthritis and ankylosing spondylitis. RORγt is a centrally positioned transcription factor driving Th17 polarization and cytokine secretion and modulation of RORγt may thus provide additional benefit to patients.
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