Plasma neuron specific enolase (NSE), tumour necrosis factor-alpha (TNF-α) and soluble IL-2receptor alpha (sIL-2Rα) levels in children with developmental delay (DD): Use of combined ROC curves to increase their diagnostic value. Developmental delay (DD) occurs when children fail to reach developmental milestones in comparison to peers of the same age range. However, there are no valuable
A Chemically Inducible IL-2Receptor Signaling Complex Allows for Effective In Vitro and In Vivo selection of Engineered CD4+ T cells. Engineered T cells represent an emerging therapeutic modality. However, complex engineering strategies can present a challenge for enriching and expanding therapeutic cells at clinical scale. Additionally, lack of in vivo cytokine support can lead to poor
IL-2receptor engineering enhances regulatory T cell function suppressed by calcineurin inhibitor. Clinical trials utilizing regulatory T cell (Treg) therapy in organ transplantation have shown promising results, however, the choice of a standard immunosuppressive regimen is still controversial. Calcineurin inhibitors (CNIs) are one of the most common immunosuppressants for organ transplantation
Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2receptor system facilitates transplantation tolerance. Adoptive transfer of Tregs has been shown to improve alloengraftment in animal models. However, it is technically challenging to expand Tregs ex vivo for the purpose of infusing large numbers of cells in the clinic. We demonstrate an innovative approach to engineering an orthogonal IL-2/IL-2receptor (IL-2R) pair, the parts of which selectively interact with each other, transmitting native IL-2 signals, but do not interact with the natural IL-2 or IL-2R counterparts, thereby enabling selective stimulation of target cells in vivo. Here, we introduced this orthogonal IL-2R into Tregs. Upon adoptive transfer in a murine mixed hematopoietic chimerism model, orthogonal IL-2
YKL-40, Soluble IL-2Receptor, Angiotensin Converting Enzyme and C-Reactive Protein: Comparison of Markers of Sarcoidosis Activity The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients and to analyse chitinase-3-like protein 1 (YKL-40), soluble interleukin-2 receptor (sIL-2R), neopterin concentrations and adenosine
89Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2receptor-binding Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2receptor (IL-2R) α binding. We describe the biodistribution and tumor accumulation of Zr-labeled
Critical Role of TGF-β and IL-2Receptor Signaling in Foxp3 Induction by an Inhibitor of DNA Methylation Under physiological conditions, CD4 regulatory T (Treg) cells expressing the transcription factor Foxp3 are generated in the thymus [thymus-derived Foxp3 Treg (tTregs) cells] and extrathymically at peripheral sites [peripherally induced Foxp3 Treg (pTreg) cell], and both developmental
Sepsis markers soluble IL-2receptor and soluble CD14 subtype as potential biomarkers for complete mucosal healing in patients with inflammatory bowel disease. Novel noninvasive biomarkers with high diagnostic accuracy are required to assess mucosal healing, which is associated with sustained clinical remission, in inflammatory bowel disease. This study aimed to explore sepsis markers
Murine Th17 cells utilize IL-2receptor gamma chain cytokines but are resistant to cytokine withdrawal-induced apoptosis Adoptive cellular therapy (ACT) with the Th17 subset of CD4 T cells can cure established melanoma in preclinical models and holds promise for treating human cancer. However, little is known about the growth factors necessary for optimal engraftment and anti-tumor activity of Th17 cells. Due to the central role of IL-2receptor gamma chain (IL2Rγ-chain) cytokines (IL-2, IL-7, and IL-15) in the activity and persistence of many T cell subsets after adoptive transfer, we hypothesized that these cytokines are important for Th17 cells. We found that Th17 cells proliferated in response to IL-2, IL-7, and IL-15 in vitro. However, in contrast to many other T cell subsets
Prospective Randomized Controlled Trial of Rabbit Antithymocyte Globulin Compared With IL-2Receptor Antagonist Induction Therapy in Kidney Transplantation The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern
An essential role for IL-2receptor in regulatory T cell function Regulatory T cells (T cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T cells in their suppressor function. However, congenital deficiency in IL-2R results
Activation of the IL-2Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome? The renal podocyte plays an important role in maintaining the structural integrity of the glomerular basement membrane. We have previously reported that patients with idiopathic nephrotic syndrome (INS) have increased IL-2 production. We hypothesized that podocytes express an IL-2receptor (IL-2R) and signaling through this receptor can result in podocyte injury. To confirm the presence of the IL-2R, we tested a conditionally immortalized murine podocyte cell line by flow cytometry, qPCR, and Western blot. To test for the presence of the IL-2R in vivo, immunohistochemical staining was performed on human renal biopsies in children with FSGS and control. Podocytes were
Impaired NK-mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2receptor modulation Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) resulting from a breakdown in peripheral immune tolerance. Although a beneficial role of natural killer (NK)-cell immune-regulatory function has been proposed, it still needs attributable to a CD4(+) T-cell evasion caused by an impaired DNAX accessory molecule (DNAM)-1/CD155 interaction. Both the expression of the activating NK-cell receptor DNAM-1, a genetic alteration consistently found in MS-association studies, and up-regulation of the receptor's ligand CD155 on CD4(+) T cells are reduced in MS. Therapeutic immune modulation of IL-2receptor restores impaired immune
Essential biphasic role for JAK3 catalytic activity in IL-2receptor signaling To drive lymphocyte proliferation and differentiation, common γ-chain (γc) cytokine receptors require hours to days of sustained stimulation. JAK1 and JAK3 kinases are found together in all γc-receptor complexes, but how their respective catalytic activities contribute to signaling over time is not known. Here we
4-1BB Signaling Enhances Primary and Secondary Population Expansion of CD8+ T Cells by Maximizing Autocrine IL-2/IL-2Receptor Signaling 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily (TNFRSF), is primarily expressed on activated T cells and is known to enhance proliferation of T cells, prevent activation-induced cell death, and promote memory formation of CD8+ T cells
Plasma Levels of Soluble IL-2Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan. Interleukin (IL) -2receptor subunit α regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα (sIL-2Rα) and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic
Comparison of induction therapy with anti-thymocyte/antilymphocyte globulin or anti-IL-2receptor antibody in pediatric kidney transplantation: Comparison of induction therapy with anti-thymocyte/antilymphocyte globulin or anti-IL-2receptor antibody in pediatric kidney transplantation: Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted
Plasma concentrations of soluble IL-2receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients. Type 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function