Proteinuria and Activated T-Lymphocytes in Diabetic Nephropathy

The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, andα-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

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Internalization, lysosomal degradation and new synthesis of surface membrane CD4 in phorbol ester-activated T-lymphocytes and U-937 cells

Experimental Cell Research ◽

10.1016/0014-4827(92)90360-k ◽

1992 ◽

Vol 201 (1) ◽

pp. 160-173 ◽

Cited By ~ 57

Author(s):

C.Munck Petersen ◽

E.Ilsø Christensen ◽

B.Storstein Andresen ◽

B.K. Møller

Keyword(s):

T Lymphocytes ◽

Phorbol Ester ◽

Surface Membrane ◽

Lysosomal Degradation ◽

New Synthesis ◽

Activated T Lymphocytes

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Specific features of T- and NK-cellular immunity in chronic lymphocytic leukemia

Russian Clinical Laboratory Diagnostics ◽

10.51620/0869-2084-2021-66-6-345-352 ◽

2021 ◽

Vol 66 (6) ◽

pp. 345-352

Author(s):

Evgeniy Vladimirovich Pochtar ◽

S. A. Lugovskaya ◽

E. V. Naumova ◽

E. A. Dmitrieva ◽

A. I. Kostin ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Chronic Lymphocytic Leukemia ◽

T Lymphocytes ◽

Nk Cells ◽

Lymphocytic Leukemia ◽

Positive Trend ◽

Functional Changes ◽

Activated T Lymphocytes ◽

T Helpers

Profound immunological dysfunction is the key factor determining the development of infectious complications in chronic lymphocytic leukemia (CLL). The aim of this work is to assess the features of the subpopulation composition of T-lymphocytes (T-helpers (Th), cytotoxic T-lymphocytes (Tcyt), T regulatory cells (Treg), T-NK cells, naive Th, Th-memory, activated T-lymphocytes, TCRγδ cells) and NK cells in peripheral blood of patients with newly diagnosed chronic lymphocytic leukemia (CLL) and receiving ibrutinib therapy. Hematological and immunophenotypic studies have been performed in 30 patients with previously untreated CLL, 122 patients on ibrutinib therapy and 20 healthy donors. The subpopulation composition of T-lymphocytes (Th, Tcyt, Treg, T-NK, naive T-helpers, memory T-helpers, TCRγδ cells, activated T-lymphocytes) and NK cells has been assessed on flow cytometer (FACSCanto II (BD)) using the following panel of monoclonal antibodies: CD45, CD19, CD3, CD4, CD5, CD8, TCRγδ, CD127, CD16, CD56, CD57 CD45RA, CD45R0, HLA-DR, CD25. Compared to controls all CLL samples were found to have higher the absolute number of T-lymphocytes, NK cells and their subpopulations, T-helpers (especially of memory T-cells), cytotoxic T-cells, regulatory T-cells, TCRγδ T-cells, activated T-lymphocytes, increased cytotoxic potential of NK cells in previously untreated CLL patients. Patients who received ibrutinib therapy have registered a positive trend towards recovery of the subpopulation composition of T-lymphocytes and NK-cells. CLL patients have been found to have quantitative and functional changes in the subpopulations of T-lymphocytes and NK cells, indicating dysregulation of the immune response, and a high risk of developing infections. Monitoring of immunological parameters for ibrutinib therapy make possible to estimate impact of ibrutinib on the adaptive anti-CLL immune response.

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Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium

Biochemical Journal ◽

10.1042/bj20050285 ◽

2005 ◽

Vol 389 (2) ◽

pp. 527-539 ◽

Cited By ~ 119

Author(s):

Shasi V. Kalivendi ◽

Eugene A. Konorev ◽

Sonya Cunningham ◽

Sravan K. Vanamala ◽

Eugene H. Kaji ◽

...

Keyword(s):

Reactive Oxygen Species ◽

T Lymphocytes ◽

Fas Ligand ◽

Reactive Oxygen ◽

Nuclear Factor ◽

Oxygen Species ◽

Rat Cardiomyocytes ◽

Activated T Lymphocytes ◽

Pre Treatment ◽

Fas L

Doxorubicin (DOX), a widely used antitumour drug, causes dose-dependent cardiotoxicity. Cardiac mitochondria represent a critical target organelle of toxicity during DOX chemotherapy. Proposed mechanisms include generation of ROS (reactive oxygen species) and disturbances in mitochondrial calcium homoeostasis. In the present study, we probed the mechanistic link between mitochondrial ROS and calcium in the embryonic rat heart-derived H9c2 cell line and in adult rat cardiomyocytes. The results show that DOX stimulates calcium/calcineurin-dependent activation of the transcription factor NFAT (nuclear factor of activated T-lymphocytes). Pre-treatment of cells with an intracellular calcium chelator abrogated DOX-induced nuclear NFAT translocation, Fas L (Fas ligand) expression and caspase activation, as did pre-treatment of cells with a mitochondria-targeted antioxidant, Mito-Q (a mitochondria-targeted antioxidant consisting of a mixture of mitoquinol and mitoquinone), or with adenoviral-over-expressed antioxidant enzymes. Treatment with GPx-1 (glutathione peroxidase 1), MnSOD (manganese superoxide dismutase) or a peptide inhibitor of NFAT also inhibited DOX-induced nuclear NFAT translocation. Pre-treatment of cells with a Fas L neutralizing antibody abrogated DOX-induced caspase-8- and -3-like activities during the initial stages of apoptosis. We conclude that mitochondria-derived ROS and calcium play a key role in stimulating DOX-induced ‘intrinsic and extrinsic forms’ of apoptosis in cardiac cells with Fas L expression via the NFAT signalling mechanism. Implications of ROS- and calcium-dependent NFAT signalling in DOX-induced apoptosis are discussed.

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The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

Veterinaria México OA ◽

10.21753/vmoa.4.3.441 ◽

2017 ◽

Vol 4 (3) ◽

Cited By ~ 1

Author(s):

Ana G. Serrato López ◽

Juan J. Montesinos Montesinos ◽

Santiago R. Anzaldúa Arce

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Veterinary Medicine ◽

T Lymphocytes ◽

Nk Cells ◽

Domestic Animals ◽

Clinical Tool ◽

Cellular Contact ◽

Activated T Lymphocytes

Mesenchymal stem cells (MSCs) have been isolated from the endometrium of humans, mice, cows, pigs and ewes. Typically, these cells are detected in the deep regions of the endometrium, closer to the union with the myometrium. MSCs possess characteristics such as clonogenicity and multipotentiality since they can differentiate in vitro into adipogenic, chondrogenic and osteogenic lineages. These cells can be induced to differentiate in vitro not only into the mesodermal lineage but also into the endodermal and ectodermal lineages. Therefore, MSCs show a great regenerative capacity for various organs and tissues, including the endometrium. Some advantages of endometrial MSCs compared with other MSC sources are their immune modulating activity, their ease of obtainment, and the amount of sample that may be collected. The study of endometrial MSCs in domestic animals is a new and promising field because increasing our understanding of the physiology and biology of these cells may lead to a better understanding of the physiopathology of reproductive diseases, and the development of treatment methods for infertility problems. In other veterinary medicine fields, MSCs can be used for the treatment of autoimmune diseases, cardiac affections, musculoskeletal and articular lesions, muscle degeneration, type 1 diabetes, urinary tract diseases, neurodegenerative processes and tumours. Finally, MSCs are also an important clinical tool for tissue engineering and regenerative medicine. The aim of this review is to present an updated outlook of the knowledge regarding endometrial MSCs and their possible applications in veterinary medicine.Figure 1: Immunoregulatory ability of MSCs. MSCs regulate the functions of NK cells, dendritic cells (DC) and T lymphocytes. The immunosuppressive effect may occur through the secretion of different factors or through cellular contact (black arrows). The former pathway involves TGFß, HGF, IL-10, PGE2, and HLA-G5, whereas the latter pathway involves the products of IDO enzyme activity, PD-L1, HLA-G1, ICAM-I and VCAM-I. Pro-inflammatory cytokines (IFN-?) secreted by NK cells and activated T lymphocytes favour the immunoregulatory activity of MSCs (dotted lines), because they increase or induce the secretion of molecules that regulate the functions of the distinct cellular components of the immune system. Modified from Montesinos et al, and Ma et al.19,66

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Resistance to ABT-737 in activated T lymphocytes: molecular mechanisms and reversibility by inhibition of the calcineurin–NFAT pathway

Cell Death and Disease ◽

10.1038/cddis.2012.38 ◽

2012 ◽

Vol 3 (4) ◽

pp. e299-e299 ◽

Cited By ~ 21

Author(s):

P E Cippà ◽

A K Kraus ◽

M T Lindenmeyer ◽

J Chen ◽

A Guimezanes ◽

...

Keyword(s):

T Lymphocytes ◽

Molecular Mechanisms ◽

Activated T Lymphocytes

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99mTc Labelling of Interleukin-2 for in Vivo Targeting of Activated T-Lymphocytes

Radiolabeled Blood Elements ◽

10.1007/978-1-4615-2462-5_9 ◽

1994 ◽

pp. 49-52

Author(s):

M. Chianelli ◽

S. J. Mather ◽

A. Signore ◽

G. Ronga ◽

P. Pozzilli ◽

...

Keyword(s):

T Lymphocytes ◽

Interleukin 2 ◽

Activated T Lymphocytes ◽

99Mtc Labelling

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Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis

Thrombosis and Haemostasis ◽

10.1160/th11-02-0110 ◽

2011 ◽

Vol 106 (12) ◽

pp. 1117-1126. ◽

Cited By ~ 13

Author(s):

Brigitta Buttari ◽

Linda Petrone ◽

Elisabetta Straface ◽

Lucrezia Gambardella ◽

Donatella Pietraforte ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Red Blood Cells ◽

Blood Cells ◽

Healthy Subjects ◽

Carotid Atherosclerosis ◽

Cell Function ◽

Inflammatory Responses ◽

Activated T Lymphocytes

SummaryOxidative stress and immune/inflammatory responses are key pathogenetic factors of atherosclerotic disease. In this contest, mechanisms that regulate survival and death of immune cells may be relevant. Previous studies have demonstrated that red blood cells (RBCs) are physiologically able to inhibit apoptosis and to promote proliferation of activated T lymphocytes from healthy subjects. The aim of the present study was to evaluate whether RBCs from patients with carotid atherosclerosis maintain their property to modulate T cell homeostasis. Peripheral blood lymphocytes (PBLs) obtained from healthy subjects were activated in vitro by phytohemagglutinin in the presence/absence of RBCs from patients with carotid atherosclerosis or of in vitro oxidised RBCs from healthy subjects. Levels of reactive oxygen species (ROS) and aging markers of RBCs as well as susceptibility to apoptosis of PBLs were evaluated by flow cytometry. PBL proliferation was evaluated by 3H-methyl-thymidine incorporation assay whereas secretion of cytokines, analysed in view of their key role in T cell function, was assessed by ELISA. Levels of ROS and phosphatidyl-serine externalisation, a sign of RBC aging, resulted significantly higher in RBCs from patients than in those from healthy subjects, whereas surface glycophorin A expression and reduced glutathione content did the opposite. Unlike RBCs obtained from healthy subjects, RBCs from patients and in vitro oxidised RBCs did not protect activated T lymphocytes from apoptosis. Hence, RBCs from patients with carotid atherosclerosis, probably due to their oxidative imbalance, impact T cell integrity and function. Our results suggest a new regulatory role for RBCs in atherosclerosis.

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