CD4+CD25+ regulatory T cells (T(REG)) are engaged in the regulation of murine and human immune responses as well as graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation. Despite their suppression of GvHD they do not impair graft-versus-tumor activity in the mouse, which makes T(REG) especially attractive candidates for cellular immunotherapy. T(REG) comprise only 5% to 10% of CD4+ T cells in peripheral blood and are naturally anergic, which prevented their use as therapeutic suppressor cells in the context of autoimmune or alloimmune reactions so far. We therefore developed an in vitro expansion protocol for human T(REG), breaking their anergy with anti-CD3/anti-CD28-coupled paramagnetic beads and a combination of interleukin (IL)-2 and IL-15. Highly purified human T(REG) can be expanded 285-fold to 1000-fold within 20 days and keep their phenotype as well as all their suppressor functions even in the context of stimulation with mature allogeneic dendritic cells. However, we demonstrate that FoxP3 is not a reliable marker for human T(REG) as it is transiently inducible in CD4+CD25- cells upon activation with cytokines or via their T cell receptor. In addition, we successfully expanded CD4+CD25+ cells from patients after allogeneic stem-cell transplantation with or without GvHD and show that different suppressor functions might be lost independently, demonstrating that human T(REG) biology is likely more complicated than previously thought.
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http://dx.doi.org/10.1097/01.cji.0000203080.43235.9e | DOI Listing |
Front Immunol
January 2025
Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease. Patients with UC typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear.
Methods: This study first analyzed RNA- seq data from public databases of humans and mice, and cytology experiments were conducted to induce or inhibit the expression of SIRT1.
J Asthma Allergy
January 2025
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Background: The role of memory B cells and their subgroups in allergic rhinitis (AR) and allergen immunotherapy (AIT) remains unclear. This study aimed to investigate the characteristics of memory B cells in the circulation of patients with AR and those undergoing AIT, as well as their clinical significance.
Methods: This study involved a cohort comprising 32 healthy control subjects, 39 individuals diagnosed with AR, and 31 AR patients who had received AIT for over one year.
Mol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, Japan.
Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes.
View Article and Find Full Text PDFIntroduction: Crohn's disease (CD) is a chronic, immune-mediated inflammatory bowel disease (IBD), presenting with symptoms of abdominal pain and bleeding from the gastrointestinal tract. There is no known cure. In vitro-expanded 'thymus-derived' regulatory T cells (tTreg) have shown promise in preclinical models of IBD, leading to interest in their use as a potential therapy in CD.
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