Influence of metal ions on human lymphocytes and the generation of titanium-specific T-lymphocytes

2011 ◽  
Vol 9 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Erwin Chan ◽  
Dieter Cadosch ◽  
Oliver P. Gautschi ◽  
Kai Sprengel ◽  
Luis Filgueira
2012 ◽  
Vol 215 (3) ◽  
pp. S63-S64
Author(s):  
Dieter Cadosch ◽  
Erwin Chan ◽  
P. Oliver Gautschi ◽  
Luis Filgueira ◽  
Hans-Peter Simmen

1999 ◽  
Vol 189 (11) ◽  
pp. 1735-1746 ◽  
Author(s):  
Derya Unutmaz ◽  
Vineet N. KewalRamani ◽  
Shana Marmon ◽  
Dan R. Littman

Lentiviral vectors have been advocated to be effective vehicles for the delivery and stable expression of genes in nondividing primary cells. However, certain cell types, such as resting T lymphocytes, are resistant to infection with HIV-1. Establishing parameters for stable gene delivery into primary human lymphocytes and approaches to overcome the resistance of resting T cells to HIV infection may permit potential gene therapy applications, genetic studies of primary cells in vitro, and a better understanding of the stages of the lentiviral life cycle. Here we demonstrate that an HIV-1–derived vector can be used for stable delivery of genes into activated human T cells as well as natural killer and dendritic cells. Remarkably, a sizeable fraction of resting T cells was stably transduced with the HIV-1 vector when cultured with the cytokine interleukin (IL)-2, IL-4, IL-7, or IL-15, or, at a lower level, with IL-6, in the absence of any other stimuli. Resting T cells stimulated with these cytokines could also be infected with replication-competent HIV-1. To test the utility of this system for performing structure–function analysis in primary T cells, we introduced wild-type as well as a mutant form of murine CD28 into human T cells and showed a requirement for the CD28 cytoplasmic domain in costimulatory signaling. The ability to stably express genes of interest in primary T cells will be a valuable tool for genetic and structure–function studies that previously have been limited to transformed cell lines. In addition, the finding that cytokine signals are sufficient to permit transduction of resting T cells with HIV may be relevant for understanding mechanism of HIV-1 transmission and pathogenesis.


2006 ◽  
Vol 13 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Anyuan Sun ◽  
Haiming Wei ◽  
Rui Sun ◽  
Weihua Xiao ◽  
Yongguang Yang ◽  
...  

ABSTRACT Human nonobese diabetic-severe combined immune deficiency (NOD-SCID) mouse chimeras have been widely used as an in vivo model to assess human immune function. However, only a small fraction of transferred human T lymphocytes can be detected in human peripheral blood lymphocyte (huPBL)-NOD-SCID chimeras. To improve the reconstitution of human T lymphocytes in NOD-SCID mice, the use of recombinant human interleukin-15 (rhIL-15) as a stimulator of human lymphocytes was explored. Administration of rhIL-15 after transplantation of huPBLs into NOD-SCID mice increased reconstitution of human T lymphocytes in a dose-dependent manner, with an optimal dosage of 1 μg/mouse. The number of human T lymphocytes (HLA-ABC+ CD3+) in the lymphoid organs or tissue of rhIL-15-treated huPBL-NOD-SCID mice increased 11- to 80-fold, and phytohemagglutinin-induced T-lymphocyte proliferation and cytokine production were significantly enhanced. Additionally, although mature human cells have not been thought to enter the murine thymus, human T lymphocytes were detected in the huPBL-NOD-SCID thymus after rhIL-15 treatment. Thus, rhIL-15 can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful in clinical treatment of T-cell deficiencies.


Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1334-1340 ◽  
Author(s):  
N.C. Munshi ◽  
R. Govindarajan ◽  
R. Drake ◽  
L.M. Ding ◽  
R. Iyer ◽  
...  

Abstract A graft-versus-leukemia (GVL) effect has been considered a major factor responsible for cures in patients with hematologic malignancies undergoing allogeneic bone marrow transplantation; however, associated graft-versus-host disease (GVHD) results in significant morbidity and mortality. T-cell depletion reduces the incidence and severity of GVHD but eliminates, at least partially, the GVL effect. Reinfusion of donor T lymphocytes at relapse posttransplantation can induce a potent antitumor response, but GVHD still occurs in the majority of patients. Prior transduction of T lymphocytes with the suicide gene, the viral thymidine kinase (TK), permits specific cell kill on administration of ganciclovir (GCV). Therefore, infusion of TK-transduced T lymphocytes may induce GVL effect and allow for their subsequent selective elimination in case GVHD develops. To evaluate the efficacy and feasibility of this promising approach, anti-CD3–stimulated primary human lymphocytes cultured in interleukin-2 were TK-transduced by a retroviral vector carrying both TK and neomycin-resistance genes. After selection in G418, more than 90% of the cells contained the TK gene as shown by a semiquantitative polymerase chain reaction. In addition, 1 to 5 days of GCV exposure, at clinically achievable concentrations of 20 to 50 μmol/L, induced ≥90% killing of G418-selected cells without affecting nontransduced cells. Correlation of the extent of T-cell kill and the proportion of TK-gene–transduced cells is consistent with the absence of a bystander effect. Transduced cells were CD3+ and either CD8+ or CD4+ and retained functional properties of untransduced cells. In vivo administration of GCV prevented tumor development after subcutaneous injection of TK-transduced murine myeloma cells (MOPC-11), whereas such an effect was not observed on injection of untransduced cells into the opposite flank. Our studies provide critical information that (1) adequate numbers of TK-transduced lymphocytes can be selected efficiently with ≥90% purity, (2) selected cells remain functional, (3) 24 hours of exposure to GCV at clinically achievable concentration effects ≥90% killing of selected cells, and (4) GCV is effective in vivo in killing TK-transduced cells. Based on these data, a clinical study has been initiated in patients with multiple myeloma with persistent or relapsing disease after T-cell–depleted allogeneic transplants.


2017 ◽  
Vol 114 (37) ◽  
pp. 9954-9959 ◽  
Author(s):  
Laurie Pinaud ◽  
Fatoumata Samassa ◽  
Ziv Porat ◽  
Mariana L. Ferrari ◽  
Ilia Belotserkovsky ◽  
...  

The enteroinvasive bacteriumShigellais a facultative intracellular bacterium known, in vitro, to invade a large diversity of cells through the delivery of virulence effectors into the cell cytoplasm via a type III secretion system (T3SS). Here, we provide evidence that the injection of T3SS effectors does not necessarily result in cell invasion. Indeed, we demonstrate through optimization of a T3SS injection reporter that effector injection without subsequent cell invasion, termed the injection-only mechanism, is the main strategy used byShigellato target human immune cells. We show that in vitro-activated human peripheral blood B, CD4+T, and CD8+T lymphocytes as well as switched memory B cells are mostly targeted by the injection-only mechanism. B and T lymphocytes residing in the human colonic lamina propria, encountered byShigellaupon its crossing of the mucosal barrier, are also mainly targeted by injection-only. These findings reveal that cells refractory to invasion can still be injected, thus extending the panel of host cells manipulated to the benefit of the pathogen. Future analysis of the functional consequences of the injection-only mechanism toward immune cells will contribute to the understanding of the priming of adaptive immunity, which is known to be altered during the course of naturalShigellainfection.


1984 ◽  
Vol 223 (1) ◽  
pp. 255-258 ◽  
Author(s):  
E Schön ◽  
H U Demuth ◽  
A Barth ◽  
S Ansorge

Glycylproline p-nitroanilide is hydrolysed in lymphocytes from human blood exclusively by dipeptidyl peptidase IV. This was demonstrated by specific inhibition with N-alanylprolyl-O-(4-nitrobenzoyl)hydroxylamine and di-isopropyl phosphorofluoridate and by studying the membrane localization of dipeptidyl peptidase IV and determining specific dipeptidyl peptidase II activity. Additional evidence that dipeptidyl peptidase IV is a marker for T-lymphocytes, obtained from determinations of biochemical activity on intact lymphocyte preparations and correlation studies with other T-cell markers, is also presented.


1996 ◽  
Vol 24 (1) ◽  
pp. 84-87 ◽  
Author(s):  
Y Ozkul ◽  
A Erenmemisoglu ◽  
A Ekecik ◽  
C Saatci ◽  
S Ozdamar ◽  
...  

The genetic toxicity of non-steroidal anti-inflammatory drugs was investigated using the sister chromatid exchange technique in cultured human lymphocytes. A total of 48 patients were treated with non-steroidal anti-inflammatory drugs (ibuprofen, ketoprofen, naproxen, indomethacin, diclofenac or acetylsalicylic acid) for 2 weeks. The average numbers of sister chromatid exchanges in cultured lymphocytes from the patients, before and after treatment with these drugs, did not differ significantly ( P > 0.05). These results indicate that treatment with non-steroidal anti-inflammatory drugs for 2 weeks does not induce sister chromatid exchanges in T lymphocytes.


2016 ◽  
Vol 115 (10) ◽  
pp. 1699-1710 ◽  
Author(s):  
Christopher T. Ford ◽  
Siân Richardson ◽  
Francis McArdle ◽  
Silvina B. Lotito ◽  
Alan Crozier ◽  
...  

AbstractDiets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation.


1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S77-S81
Author(s):  
K. H. Usadel ◽  
J. Teuber ◽  
R. Paschke ◽  
M. Junker ◽  
U. Schwedes

Abstract. After transplantation of human tissue to nu/nu mice the human lymphocytes disappear. In this context, interestingly, the DR-expression is not detectable anymore after transplantation of the tissues from patients with autoimmune thyrotoxicosis and cancer. Neopterin release was only demonstrable when T-lymphocytes from patients with autoimmune thyrotoxicosis or PHA-stimulated lymphocytes were added, independently of the presence of DR-expression in the used culture tissues. These results seem to exclude a functional role of DR-expression as a trigger mechanism of autoimmunity. It is supposed that DR-priming on epithelial cells is mediated by kinine production of activated T-lymphocytes or macrophages.


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