Vβ8+ T cells protect from demyelinating disease in a viral model of multiple sclerosis

Drescher, Kristen M.; Johnston, Sean L.; Hogancamp, William E.; Nabozny, Gerald H.; David, Chella S.; Rimm, Ilonna J.; Wettstein, Peter J.; Rodriguez, Moses

doi:10.1093/intimm/12.3.271

Cited by 9 publications

(4 citation statements)

References 49 publications

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“…Preferential usage of TCRVβ20 is associated with Staphylococcus aureus infection and cutaneous lymphoma. [26][27][28] Among TACI-CVID and non-TACI-CVID patients only 1 patients had a malignant disease. None of the patients had a Staphylococcus aureus infection.…”

Section: Discussionmentioning

confidence: 99%

Flow Cytometric Analysis of T Cell Vβ Repertoire in Common Variable Immunodeficiency Patients with TACI Mutations

Halaçlı¹,

Özbek²,

Aytekin³

et al. 2021

TJI

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Objective: TCR (T Cell Receptor) which is expressed on T cells is responsible for recognizing antigens presented by HLA molecules of the APCs (Antigen Presenting Cells) and initiation of the immune response. It has been reported that TACI (Transmembrane activator and calcium modulating cyclophilin ligand interactor) mediates the interaction of B cells and dendritic cells which are both responsible for the processing of T cells. Materials and Methods: In this study, 24 TCRVβ clones were analyzed by using multiparametric flow cytometry in seven patients with TACI mutation [two homozygous (c.310T> C) five heterozygous (c.310T> C, c.226G> C, c.260T> A)], four CVID (Common Variable Immunodeficiency) patients who had not TACI defect (non-TACI) and five healthy controls. In this study group, serum Ig levels and infection history, CD4+ and CD8+ cell percentages, and HLA profiles were investigated. Results: Increased TCRVβ13.2 clone was observed in patients with TACI defects unlike control individuals and non-TACI-CVID patients (p=0.02). We found that there was a statistically significant decrease in TCRVβ8 clone (p=0.012) in TACI deficient CVID patients and non-TACI-CVID patients compared to control individuals. TCRVβ20 clones in non-TACI-CVID patients were decreased compared to TACI-CVID patients and control individuals (p=0.009). Decreased TCRVβ8 was also associated with TACI deficient CVID patients. Conclusion: Further studies and large cohorts are needed to understand the relationship between TCRVβ8, TCRVβ13.2, and CVID with TACI mutations.

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Section: Discussionmentioning

confidence: 99%

Flow Cytometric Analysis of T Cell Vβ Repertoire in Common Variable Immunodeficiency Patients with TACI Mutations

Halaçlı¹,

Özbek²,

Aytekin³

et al. 2021

TJI

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“…Studien zur Demyelinisierung durch Theilers murine encephalomyelitis virus, ebenfalls ein Modell für Multiple Sklerose, weisen auf eine schützende Wirkung von Vâ8 + Zellen hin [11]. Für CD8 + Zellen von PsoriasisErkrankten ist bekannt, dass sie vorwiegend Vâ3 und Vâ13.1 Gene verwenden [10].…”

Section: Tcr Und Erkrankungunclassified

T-Cell Receptor and Allergy - A Survey

Liebers

Raulf‐Heimsoth²

2001

Pneumologie

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Das Immunsystem stellt ein hochentwickeltes Abwehrsystem der Wirbeltiere dar, an dem viele verschiedene Zelltypen beteiligt sind. Eine entscheidende Rolle spielen dabei die Lymphozyten mit ihren Antigenrezeptoren. Sie sind für die Spezifität der Reaktionen verantwortlich. B-, T-und NK-Zellen sind die wesentlichen Lymphozytenpopulationen, die unterschieden werden. T-Zellen haben wichtige regulatorische Funktionen. Sie unterstützen als T-Helfer-Zellen bestimmte Immunantworten, z. B. die Immunglobulinproduktion. Die zytotoxischen T-Zellen sind dagegen in direkte Effektorfunktionen involviert, z. B. in die Lyse Virus-infizierter Zellen.

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“…Within the CNS, both specific and nonspecific T cells can patrol and act either beneficially (7,8) or detrimentally (9). For example, T cells in the brain are crucial and beneficial when they combat and clear encephalomyelitis-inducing viruses from the CNS (7,8).…”

mentioning

confidence: 99%

TCR Activation Eliminates Glutamate Receptor GluR3 from the Cell Surface of Normal Human T Cells, via an Autocrine/Paracrine Granzyme B-Mediated Proteolytic Cleavage

Ganor

Teichberg

Levite

2007

The Journal of Immunology

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The majority of resting normal human T cells, like neuronal cells, express functional receptors for glutamate (the major excitatory neurotransmitter in the CNS) of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor subtype 3 (GluR3). Glutamate by itself (∼10 nM) activates key T cell functions, including adhesion to fibronectin and laminin and chemotactic migration toward CXCL12/stromal cell-derived factor 1. In this study, we found by GluR3-specific immunostaining, flow cytometry, and Western blots that GluR3 cell surface expression decreases dramatically following TCR activation of human T cells. CXCR4, VLA-4, and VLA-6 also decrease substantially, whereas CD147 increases as expected, after TCR activation. Media of TCR-activated cells “eliminates” intact GluR3 (but not CXCR4 and VLA-6) from the cell surface of resting T cells, suggesting GluR3 cleavage by a soluble factor. We found that this factor is granzyme B (GB), a serine protease released by TCR-activated cells, because the extent of GluR3 elimination correlated with the active GB levels, and because three highly specific GB inhibitors blocked GluR3 down-regulation. Media of TCR-activated cells, presumably containing cleaved GluR3B peptide (GluR3 aa 372–388), inhibited the specific binding of anti-GluR3B mAb to synthetic GluR3B peptide. In parallel to losing intact GluR3, TCR-activated cells lost glutamate-induced adhesion to laminin. Taken together, our study shows that “classical immunological” TCR activation, via autocrine/paracrine GB, down-regulates substantially the expression of specific neurotransmitter receptors. Accordingly, glutamate T cell neuroimmune interactions are influenced by the T cell activation state, and glutamate, via AMPA-GluR3, may activate only resting, but not TCR-activated, T cells. Finally, the cleavage and release to the extracellular milieu of the GluR3B peptide may in principle increase its antigenicity, and thus the production, of anti-self GluR3B autoantibodies, which activate and kill neurons, found in patients with various types of epilepsy.

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Vβ8+ T cells protect from demyelinating disease in a viral model of multiple sclerosis

Cited by 9 publications

References 49 publications

Flow Cytometric Analysis of T Cell Vβ Repertoire in Common Variable Immunodeficiency Patients with TACI Mutations

Flow Cytometric Analysis of T Cell Vβ Repertoire in Common Variable Immunodeficiency Patients with TACI Mutations

T-Cell Receptor and Allergy - A Survey

TCR Activation Eliminates Glutamate Receptor GluR3 from the Cell Surface of Normal Human T Cells, via an Autocrine/Paracrine Granzyme B-Mediated Proteolytic Cleavage

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