scholarly journals Acellular Wharton’s Jelly, Potentials in T-Cell Subtypes Differentiation, Activation and Proliferation

2020 ◽  
Vol 10 (4) ◽  
pp. 617-622
Author(s):  
Mehdi Talebi ◽  
Hojjatollah Nozad Charoudeh ◽  
Ali Akbar Movassaghpour Akbari ◽  
Behzad Baradaran ◽  
Tohid Kazemi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Culture Media ◽  
Cell Activity ◽  
Cell Subset ◽  
Wharton’S Jelly ◽  
Cellular Immunotherapy ◽  
Lag Phase ◽  
Wharton's Jelly ◽  
Study Results

Purpose : Because of different potentials of T-cell subtypes in T-cell based cellular immunotherapy approaches such as CAR-T cell therapies; Regarding the high cost of the serum-free specific culture media, having distinct control on T-cell subset activation, expansion and differentiation seem crucial in T-cell expansion step of cell preparation methods. By the way, there was no clear data about the effect of acellular Wharton’s Jelly (AWJ) on T-cells expansion, activation or differentiation status. So, we have launched to study the effect of AWJ on T-cell’s immunobiological properties. Methods: CD3+ T-cells were isolated from healthy bone marrow allogeneic donors, sorted by FACS method and cultured on either routine phyto-hemagglutinin complemented and different concentrations of AWJ, lag phase and doubling time of the cells calculated from cell growth curve. After 3, 7 and 14-days T-cell subtypes cell markers and cell activity related genes expression rate have been evaluated by flow cytometry and real-time polymerase chain reaction (PCR) methods respectively. Results: AWJ in a 1:1 ratio compared with contemporary lymphocyte culture media showed significant activating and proliferative capacities. The introduced condition has not affected the frequency of CD4+ subpopulation of T-cells, but significantly increased even CD8+ cells and immune-activator genes in T-cells. The regulatory and memory subsets of T-cells in this study have not affected significantly. Conclusion: the study results revealed that AWJ can be utilized as a supportive substance to increase the memory properties of the T-cells, gives control to design a selective medium for expanding and differentiating memory T-cells, relatively.

6,7,4′-Trihydroxyflavanone Prevents Methamphetamine-Induced T Cell Deactivation by Protecting the Activated T Cells from Apoptosis

2021 ◽  
pp. 1-17
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Activated T Cells ◽  
Study Results ◽  
Apoptotic Proteins ◽  
Pre Treatment

Methamphetamine (METH) is an extremely addictive drug that has raised serious public health concerns recently. METH addiction not only results in neuronal cytotoxicity, but it also affects immune cell activity, including T lymphocytes. 6,4,7[Formula: see text]-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been studied for its antibacterial activity, but evidence for whether THF has an anti-cytotoxic and protective effect on T cell activation exposed to METH is lacking. In this study, results showed that treatment with THF was not cytotoxic to Jurkat T cells but dose-dependently mitigated the cytotoxicity induced by exposure to METH. The Western blot results demonstrating pre-treatment with THF maintained the expression of anti-apoptotic proteins and phosphorylation of PI3K/Akt/mTOR downregulated by treatment with METH. Furthermore, we found that decreased expression of IL-2 and CD69 by METH exposure was partially restored, and viability was significantly prevented by pre-treatment with THF in activated T cells. These findings were involved in re-elevated expression of anti-apoptotic proteins as well as recovered pathways including MAPK/PI3K/Akt/mTOR in activated T cells pre-exposed to METH. Our results suggest beneficial effects of THF against the cytotoxic and immune-modulating effect of METH on T cells and therapeutic potential of THF for patients with immunodeficiency caused by METH addiction.

scholarly journals Modular Chimeric Antigen Receptor Systems for Universal CAR T Cell Retargeting

2020 ◽  
Vol 21 (19) ◽  
pp. 7222
Author(s):  
Ashley R. Sutherland ◽  
Madeline N. Owens ◽  
C. Ronald Geyer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Cellular Immunotherapy ◽  
Antigen Receptors ◽  
Antigen Specificity ◽  
Precise Control ◽  
Car T Cells ◽  
Multiple Antigen ◽  
Car T

The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells. In this review, we summarize developments in universal or modular CAR T strategies that expand on current CAR T systems and open the door for more customizable T cell activity.

scholarly journals High-Fat Diet Alters Immunogenic Properties of Circulating and Adipose Tissue-Associated Myeloid-Derived CD45+DDR2+ Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Sara J. Sidles ◽  
Ying Xiong ◽  
M. Rita I. Young ◽  
Amanda C. LaRue
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Activity ◽  
Cell Subset ◽  
Total Body Weight ◽  
T Cell Subsets ◽  
Activation Markers

Chronic inflammation is evident in the adipose tissue and periphery of patients with obesity, as well as mouse models of obesity. T cell subsets in obese adipose tissue are skewed towards Th1- and Th17-associated phenotypes and their secreted cytokines contribute to obesity-associated inflammation. Our lab recently identified a novel, myeloid-derived CD45+DDR2+ cell subset that modulates T cell activity. The current study sought to determine how these myeloid-derived CD45+DDR2+ cells are altered in the adipose tissue and peripheral blood of preobese mice and how this population modulates T cell activity. C57BL/6 mice were fed with a diet high in milkfat (60%·kcal, HFD) ad libitum until a 20% increase in total body weight was reached, and myeloid-derived CD45+DDR2+ cells and CD4+ T cells in visceral adipose tissue (VAT), mammary gland-associated adipose tissue (MGAT), and peripheral blood (PB) were phenotypically analyzed. Also analyzed was whether mediators from MGAT-primed myeloid-derived CD45+DDR2+ cells stimulate normal CD4+ T cell cytokine production. A higher percentage of myeloid-derived CD45+DDR2+ cells expressed the activation markers MHC II and CD80 in both VAT and MGAT of preobese mice. CD4+ T cells were preferentially skewed towards Th1- and Th17-associated phenotypes in the adipose tissue and periphery of preobese mice. In vitro, MGAT from HFD-fed mice triggered myeloid-derived CD45+DDR2+ cells to induce CD4+ T cell IFN-γ and TNF-α production. Taken together, this study shows that myeloid-derived CD45+DDR2+ cells express markers of immune activation and suggests that they play an immune modulatory role in the adipose tissue of preobese mice.

scholarly journals Inducible gene switches with memory in human T cells for cellular immunotherapy

2018 ◽  
Author(s):  
Deboki Chakravarti ◽  
Leidy D Caraballo ◽  
Benjamin H. Weinberg ◽  
Wilson W. Wong
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Adoptive T Cell Therapy ◽  
Cellular Immunotherapy ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Gene Switches ◽  
Engineered T Cells

AbstractCell-based therapies that employ engineered T cells—including the expression of chimeric antigen receptors (CARs)—to target cancer cells have demonstrated promising responses in clinical trials. However, engineered T cell responses must be regulated to prevent severe side effects such as cytokine storms and off-target responses. Here we present a class of recombinase-based gene circuits that will enable inducible switching between two states of adoptive T cell therapy using an FDA-approved drug, creating a generalizable platform that can be used to control when and how strongly a gene is expressed. These circuits exhibit memory such that induced T cells will maintain any changes made even when the drug inducer is removed. This memory feature avoids prolonged drug inducer exposure, thus reducing the complexity and potential side effect associated with the drug inducer. We have utilized these circuits to control the expression of an anti-Her2-CAR, demonstrating the ability of these circuits to regulate CAR expression and T cell activity. We envision this platform can be extended to regulate other genes in T cell behavior for various adoptive T cell therapies.

scholarly journals iNKT cells coordinate immune pathways to enable engraftment in nonconditioned hosts

2021 ◽  
Vol 4 (7) ◽  
pp. e202000999
Author(s):  
Nicholas J Hess ◽  
Nikhila S Bharadwaj ◽  
Elizabeth A Bobeck ◽  
Courtney E McDougal ◽  
Shidong Ma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Progenitor Cell ◽  
Inflammatory Responses ◽  
Cell Activity ◽  
Cellular Immunotherapy ◽  
Human Umbilical Cord ◽  
Inkt Cells ◽  
Hematopoietic Stem

Invariant natural killer T (iNKT) cells are a conserved population of innate T lymphocytes that interact with key antigen-presenting cells to modulate adaptive T-cell responses in ways that can either promote protective immunity, or limit pathological immune activation. Understanding the immunological networks engaged by iNKT cells to mediate these opposing functions is a key pre-requisite to effectively using iNKT cells for therapeutic applications. Using a human umbilical cord blood xenotransplantation model, we show here that co-transplanted allogeneic CD4+ iNKT cells interact with monocytes and T cells in the graft to coordinate pro-hematopoietic and immunoregulatory pathways. The nexus of iNKT cells, monocytes, and cord blood T cells led to the release of cytokines (IL-3, GM-CSF) that enhance hematopoietic stem and progenitor cell activity, and concurrently induced PGE2-mediated suppression of T-cell inflammatory responses that limit hematopoietic stem and progenitor cell engraftment. This resulted in successful long-term hematopoietic engraftment without pretransplant conditioning, including multi-lineage human chimerism and colonization of the spleen by antibody-producing human B cells. These results highlight the potential for using iNKT cellular immunotherapy to improve rates of hematopoietic engraftment independently of pretransplant conditioning.

CD4 T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favourable Prognostic Factor

2018 ◽  
Author(s):  
Shuhao Zhang ◽  
Shyamal Goswami ◽  
Jiaqiang Ma ◽  
Lu Meng ◽  
Youping Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Prognostic Factor ◽  
Regulatory T Cells ◽  
Biliary Atresia ◽  
Cell Subset ◽  
Cd4 T Cell ◽  
T Cell Subset

scholarly journals Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

2021 ◽  
Author(s):  
Shannon L. McArdel ◽  
Anne-Sophie Dugast ◽  
Maegan E. Hoover ◽  
Arjun Bollampalli ◽  
Enping Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Blood Cell ◽  
Nk Cells ◽  
Red Blood Cell ◽  
Safety Profile ◽  
Nk Cell ◽  
Cell Activity ◽  
In Vivo Studies

AbstractRecombinant agonists that activate co-stimulatory and cytokine receptors have shown limited clinical anticancer utility, potentially due to narrow therapeutic windows, the need for coordinated activation of co-stimulatory and cytokine pathways and the failure of agonistic antibodies to recapitulate signaling by endogenous ligands. RTX-240 is a genetically engineered red blood cell expressing 4-1BBL and IL-15/IL-15Rα fusion (IL-15TP). RTX-240 is designed to potently and simultaneously stimulate the 4-1BB and IL-15 pathways, thereby activating and expanding T cells and NK cells, while potentially offering an improved safety profile through restricted biodistribution. We assessed the ability of RTX-240 to expand and activate T cells and NK cells and evaluated the in vivo efficacy, pharmacodynamics and tolerability using murine models. Treatment of PBMCs with RTX-240 induced T cell and NK cell activation and proliferation. In vivo studies using mRBC-240, a mouse surrogate for RTX-240, revealed biodistribution predominantly to the red pulp of the spleen, leading to CD8 + T cell and NK cell expansion. mRBC-240 was efficacious in a B16-F10 melanoma model and led to increased NK cell infiltration into the lungs. mRBC-240 significantly inhibited CT26 tumor growth, in association with an increase in tumor-infiltrating proliferating and cytotoxic CD8 + T cells. mRBC-240 was tolerated and showed no evidence of hepatic injury at the highest feasible dose, compared with a 4-1BB agonistic antibody. RTX-240 promotes T cell and NK cell activity in preclinical models and shows efficacy and an improved safety profile. Based on these data, RTX-240 is now being evaluated in a clinical trial.

scholarly journals Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3662-3672 ◽  
Author(s):  
Nobukazu Watanabe ◽  
Stephen C. De Rosa ◽  
Anthony Cmelak ◽  
Richard Hoppe ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

scholarly journals VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

Science ◽  
2020 ◽  
Vol 367 (6475) ◽  
pp. eaay0524 ◽  
Author(s):  
Mohamed A. ElTanbouly ◽  
Yanding Zhao ◽  
Elizabeth Nowak ◽  
Jiannan Li ◽  
Evelien Schaafsma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Subset ◽  
Peripheral Tolerance ◽  
Cell Immune Response ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Naïve T Cell ◽  
Naive T Cell

Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve T cell subset and enhanced self-reactivity. Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion. Although a critical player in naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.

scholarly journals Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells.

1991 ◽  
Vol 174 (4) ◽  
pp. 891-900 ◽  
Author(s):  
S M Friedman ◽  
M K Crow ◽  
J R Tumang ◽  
M Tumang ◽  
Y Q Xu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Activity ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Mycoplasma Arthritidis ◽  
Human T Cells

While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.

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