FOXP3 is required for the generation and function of CD4(+)CD25(+) regulatory T (Treg) cells. To elucidate the biological role of Treg cells, we used a monoclonal anti-FOXP3 antibody to examine the frequencies of Treg cells during child development. The percentages of CD4(+)CD25(+)FOXP3(+) T cells were constant shortly from after birth through adulthood. CD4(+)CD25(+)FOXP3(+) T cells in cord blood showed the naive CD45RA(+)CD45RO(-) phenotype, whereas adult CD4(+)CD25(+)FOXP3(+) T cells expressed mostly the memory CD45RA(-)CD45RO(+) phenotype. The age-dependent dominance of memory CD4(+)CD25(+)FOXP3(+) T cells implies functional differences between naive and memory Treg cells. Notably, four patients with FOXP3 gene mutations revealed a paucity of CD4(+)CD25(+)FOXP3(+) T cells. Importantly, one patient with a frame shift mutation, who showed typical symptoms of IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked), exhibited marked T cell activation, whereas others with missense mutations, who were clinically milder, did not. This observation suggests a possible genotype-phenotype correlation in IPEX.
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http://dx.doi.org/10.1016/j.clim.2007.08.004 | DOI Listing |
Am J Obstet Gynecol
December 2024
Department of Gynecology, Obstetrics and Neonatology, General University Hospital in Prague and First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Nat Commun
December 2024
Division of Plastic Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Secondary lymphedema is a common sequel of oncologic surgery and presents a global health burden still lacking pharmacological treatment. The infiltration of the lymphedematous extremities with CD4T cells influences lymphedema onset and emerges as a promising therapy target. Here, we show that the modulation of CD4FOXP3CD25regulatory T (T) cells upon anti-CTLA4 treatment protects against lymphedema development in patients with melanoma and in a mouse lymphedema model.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
December 2024
Pathology Advanced Translational Research Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Background: Regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis, but their dynamics are altered in a subset of people living with Human Immunodeficiency Virus (HIV) known as immunological non-responders (INRs). INRs fail to reconstitute CD4 T-cell counts despite viral suppression. This study aimed to examine Treg dysregulation in INRs, comparing them to immunological responders (IRs) and healthy controls (HCs).
View Article and Find Full Text PDFImmunopharmacol Immunotoxicol
December 2024
Nursing Department, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia.
Background: One of the common findings in systemic sclerosis (SSc) patients has been long-term exposure to environmental toxins such as pesticides. However, the data available shows an equivocal association between pesticide exposure and autoimmunity in SSc.
Methods: We investigated the levels of organochlorine pesticides (OCPs) in blood of 20 SSc patients and 17 healthy controls, and also studied their effect on T lymphocytes and their functional responses.
Clin Transl Med
December 2024
Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.
Background: The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from individuals with and without T1D and derived into various immune cells, including macrophages and dendritic cells.
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