Cobalt-chromium-molybdenum but not titanium-6aluminium-4vanadium alloy discs inhibit human t cell activation in vitro

BioMetals ◽  
1996 ◽  
Vol 9 (4) ◽  
pp. 321-326 ◽  
Author(s):  
Cristina Faleiro ◽  
Inês Godinho ◽  
Ulrich Reus ◽  
Maria de Sousa
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cobalt Chromium ◽  
Human T Cell ◽  
Cobalt Chromium Molybdenum

scholarly journals A high-affinity human TCR-like antibody detects celiac disease gluten peptide–MHC complexes and inhibits T cell activation

2021 ◽  
Vol 6 (62) ◽  
pp. eabg4925
Author(s):  
Rahel Frick ◽  
Lene S. Høydahl ◽  
Jan Petersen ◽  
M. Fleur du Pré ◽  
Shraddha Kumari ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Human Leukocyte ◽  
Fab Fragment ◽  
Biopsy Material ◽  
Human T Cell

Antibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation and may have therapeutic potential. Here, we generated human T cell receptor (TCR)–like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-α2 in celiac disease (CeD). Phage display selection combined with secondary targeted engineering was used to obtain highly specific antibodies with picomolar affinity. The crystal structure of a Fab fragment of the lead antibody 3.C11 in complex with HLA-DQ2.5:DQ2.5-glia-α2 revealed a binding geometry and interaction mode highly similar to prototypic TCRs specific for the same complex. Assessment of CeD biopsy material confirmed disease specificity and reinforced the notion that abundant plasma cells present antigen in the inflamed CeD gut. Furthermore, 3.C11 specifically inhibited activation and proliferation of gluten-specific CD4+ T cells in vitro and in HLA-DQ2.5 humanized mice, suggesting a potential for targeted intervention without compromising systemic immunity.

scholarly journals In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Marina Aparicio-Soto ◽  
Caterina Curato ◽  
Franziska Riedel ◽  
Hermann-Josef Thierse ◽  
Andreas Luch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cross Reactivity ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Human T Cell ◽  
The Individual

Background: Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells. Methods: Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years. Results: We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was p-phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases. Interpretation: Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments.

scholarly journals Differential effects of estradiol and progesterone on human T cell activation in vitro

2021 ◽  
Author(s):  
Georgia Papapavlou ◽  
Sandra Hellberg ◽  
Johanna Raffetseder ◽  
Jan Brynhildsen ◽  
Mika Gustafsson ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Differential Effects ◽  
Human T Cell

scholarly journals GFP Affects Human T Cell Activation and Cytokine Production following In Vitro Stimulation

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e50068 ◽  
Author(s):  
Kristi A. Koelsch ◽  
YuJing Wang ◽  
Jacen S. Maier-Moore ◽  
Amr H. Sawalha ◽  
Jonathan D. Wren
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytokine Production ◽  
Human T Cell

scholarly journals Strain-Dependent Variation in Mycobacterium bovis BCG-Induced Human T-Cell Activation and Gamma Interferon Production In Vitro

2007 ◽  
Vol 75 (6) ◽  
pp. 3197-3201 ◽  
Author(s):  
Ana M. Aguirre-Blanco ◽  
Pauline T. Lukey ◽  
Jacqueline M. Cliff ◽  
Hazel M. Dockrell
Keyword(s):  
T Cell ◽  
Mycobacterium Bovis ◽  
T Cell Activation ◽  
Cell Activation ◽  
Gamma Interferon ◽  
Interferon Production ◽  
Human T Cell ◽  
Stimulatory Capacity ◽  
Strain Dependent

ABSTRACT Three commonly used Mycobacterium bovis BCG vaccine strains elicited different magnitudes of T-cell activation and gamma interferon production in vitro in healthy BCG-vaccinated individuals. Glaxo 1077 exhibited the greatest stimulatory capacity, followed by Pasteur 1173 and then Danish 1331. These differences may affect in vitro stimulation and vaccination-induced immunogenicity.

scholarly journals In vivo and in vitro phosphorylation of annexin II in T cells: potential regulation by annexin V

1995 ◽  
Vol 310 (1) ◽  
pp. 243-248 ◽  
Author(s):  
T Dubois ◽  
J P Oudinet ◽  
F Russo-Marie ◽  
B Rothhut
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cellular Proliferation ◽  
Large Family ◽  
Jurkat Cells ◽  
Human T Cell

In order to understand how signal transduction occurs during T cell activation, it is necessary to identify the key regulatory molecules whose function is influenced by phosphorylation. Annexins II (A-II) and V (A-V) belong to a large family of Ca(2+)-dependent phospholipid-binding proteins. Among many putative functions, annexins may be involved in signal transduction during cellular proliferation and differentiation. In the present study we show that A-II is phosphorylated in vivo in the Jurkat human T cell line. Indeed, A-II is phosphorylated after stimulation by phorbol myristate acetate and on serine residues after T cell antigen receptor (TcR) stimulation. In cytosol from Jurkat cells, A-II is phosphorylated only by Ca2+/phospholipid-stimulated kinases such as Ca(2+)-dependent protein kinases C (cPKCs). A-V inhibits the phosphorylation of A-II and other substrates of cPKCs and has no effect on kinases activated only by phospholipids. In conclusion, A-II is phosphorylated both in vitro and in vivo in Jurkat cells, and may play a role as a substrate during signal transduction in lymphocytes via the TcR through the PKC pathway. On the other hand, A-V could act as a potent modulator of cPKCs in Jurkat cells.

scholarly journals Methodology for in vitro Assessment of Human T Cell Activation and Blockade

BIO-PROTOCOL ◽  
2020 ◽  
Vol 10 (11) ◽  
Author(s):  
Joseph Podojil ◽  
Igal Ifergan ◽  
Ming-Yi Chiang ◽  
Joshua Meeks ◽  
Stephen Miller
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human T Cell ◽  
In Vitro Assessment

Development of a fully human t-cell engaging bispecific antibody for the treatment of multiple myeloma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 60-60
Author(s):  
Ben Buelow ◽  
Priya Choudhry ◽  
Starlynn Clarke ◽  
Kevin Dang ◽  
Laura Davison ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Bispecific Antibody ◽  
Human Pbmcs ◽  
Human T Cell

60 Background: T-cell engaging bispecific antibody (T-BsAb) therapies are highly efficacious and well suited for targets with low expression on tumor cells. Recently, T-BsAbs with high activation of CD3 have been shown to overstimulate T cells, leading to toxicity and decreased efficacy. Teneobio has developed a fully human BCMA-specific T-BsAb using a low-activating αCD3 that is highly effective in vitro and in vivo against MM but stimulates minimal cytokine release. Methods: UniRats were immunized with either CD3 or BCMA antigens and antigen-specific UniAbs were identified by Ab repertoire sequencing and high-throughput gene assembly, expression, and screening. Antigen-specific VH sequences with the desired target affinity were selected using recombinant proteins and cells. In vitro efficacy studies included T-cell activation by cytokine- and tumor cell kill by calcein-release assays. In vivo efficacy of the molecules was evaluated in NSG mice harboring myeloma cells and human PBMCs. Results: BCMA-specific UniAbs bound plasma cells with sub-nM affinity. Strong and weak T cell agonists were identified that bound human T cells with high and low affinities respectively. T-BsAbs with a strong and a weak αCD3 demonstrated T-cell activation and tumor-cell cytotoxicity in vitro; T-BsAbs with a weak αCD3 showed markedly reduced cytokine production even at doses that showed maximum tumor cell lysis. In vivo, BCMAxCD3 T-BsAbs reduced tumor load and increased survival when co-administered with human PBMCs as compared to controls. Conclusions: Our results suggest that T-BsAbs with low-activating αCD3 arms may have a favorable toxicity profile while maintaining efficacy in the treatment of MM.

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