Processing and presentation of tetanus toxin by antigen-presenting cells from patients with chronic granulomatous disease (CGD) to human specific T cell clones are not impaired

Barbey, Catherine; Tiercy, Jean‐Marie; Fairweather, Neil F.; Niemann, Heiner; Seger, Reinhard; Corradin, Giampietro

doi:10.1111/j.1365-2249.1994.tb06515.x

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…[ 3 H]thymidine incorporation was measured in a ␤-counter (Top Count; Packard Bioscience S.A., Zürich, Switzerland). T-cell cloning (0.3 cell/well) was performed as described earlier (3,36). Clones with a stimulation index of Ͼ2 were further expanded and retested for specificity as described previously (4,36).…”

Section: Methodsmentioning

confidence: 99%

Ex Vivo Monitoring of Antigen-Specific CD4⁺T Cells after Recall Immunization with Tetanus Toxoid

Barbey

Pradervand

Barbier

et al. 2007

Clin Vaccine Immunol

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To monitor antigen-specific CD4؉ T cells during a recall immune response to tetanus toxoid (TT), a sequential analysis including ex vivo phenotyping and cytokine flow cytometry, followed by cloning and T-cell-receptor (TCR) spectratyping of cytokine-positive CD4 ؉ T cells, was performed. Grossly, twice as many TT-specific CD4 ؉ T-cell clones, ex vivo derived from the CCR7 ؉ subsets appears to target the bulk of antigen-specific T cells and to reach an analytical power sufficient to adequately delineate in field trials the profile of the antigen-specific response to vaccine.Phenotypic characterization of antigen-specific CD4 ϩ T cells with distinct functional properties represents currently a major challenge in human applied experimental immunology. Ex vivo analysis of these cell populations is critical, since in vitro culture may alter composition and functional properties of the populations of interest. If major histocompatibility complex (MHC) class I tetramer/peptide complexes did greatly facilitate the analysis of antigen specific CD8 ϩ T cells, the use of MHC class II tetramer/peptide has been hampered by the complexity of MHC class II tetramer production, by the usually low CD4 ϩ T-cell precursor frequency, by an often-degenerated peptide epitope specificity, and by non-MHC class II moleculerestricted allelic expression (12,15,24,35,36). As an alternative approach to circumvent these difficulties, we here applied cytokine flow cytometry (9, 11), now extensively used to define ex vivo frequencies and phenotypic and functional characteristics of viral antigen-specific CD4 ϩ T cells (8,22,43), coupled to T-cell-receptor (TCR) spectratype analysis. Indeed, characterization of the unique complementary determining region 3 (CDR3) sequence expression of CD4 ϩ (or CD8 ϩ ) T-cell clones appears to be a sensitive method for monitoring qualitative and quantitative T-cell responses during natural infection or vaccination (21,23,45,48).In the present study, tetanus toxoid (TT) was used as a model vaccine antigen that likely shares common functional characteristics with other nonviral antigens, such as a low frequency of specific CD4 ϩ T cells in the periphery at steady state and a specific CD4 ϩ T-cell response to multiple epitope peptides presented by MHC class II molecules (16,36,40). Using ex vivo cell phenotyping and cloning in combination with TCR spectratype analysis of cytokine-positive CD4 ϩ T cells, we sought to establish experimental conditions to track ex vivo antigenspecific CD4 ϩ T cells in conditions that are likely to reflect clinical situations such as vaccination, nonviral pathogen infections, or allergic diseases.

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Section: Methodsmentioning

confidence: 99%

Ex Vivo Monitoring of Antigen-Specific CD4⁺T Cells after Recall Immunization with Tetanus Toxoid

Barbey

Pradervand

Barbier

et al. 2007

Clin Vaccine Immunol

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“…Presentation of exogenous ovalbumin but not tetanus toxoid Ag was altered in APC from CGD patients (7, 8). Neither study identified the defective oxidase subunits in the CGD patient-derived APC.…”

Section: Introductionmentioning

confidence: 99%

Cutting Edge: NADPH Oxidase Modulates MHC Class II Antigen Presentation by B Cells

Crotzer

Matute

Arias

et al. 2012

The Journal of Immunology

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Summary Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production. Defects in oxidase function result in chronic granulomatous disease (CGD) with hallmark recurrent microbial infections and inflammation. The oxidase′s role in the adaptive immune response is not well-understood. Class II presentation of cytoplasmic and exogenous Ag to CD4+ T cells was impaired in human B cells with reduced oxidase p40phox subunit expression. Naturally arising mutations which compromise p40phox function in a CGD patient also perturbed class II Ag presentation and intracellular ROS production. Reconstitution of patient B cells with wild-type, but not a mutant, p40phox allele restored exogenous Ag presentation and intracellular ROS generation. Remarkably, class II presentation of epitopes from membrane Ag was robust in p40phox-deficient B cells. These studies reveal a role for NADPH oxidase and p40phox in skewing epitope selection and T cell recognition of self Ag.

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“…In phagocytes, nitric oxide production is required for processing bacterial polysaccharides into fragments capable of binding MHC-II for presentation to T cells (52). Conflicting reports with B lymphocytes also suggest roles for superoxide and NADPH oxidase in MHC-II presentation, yet these early studies employed samples from reported CGD patients without genetic analysis to confirm defective oxidase subunits (53, 54). Although B lymphocytes express functional NADPH oxidase subunits (55), the precise function of this enzyme complex in these cells remains unclear.…”

Section: Nadph Oxidase and Mhc-ii Antigen Presentationmentioning

confidence: 99%

A Role for NADPH Oxidase in Antigen Presentation

Gardiner¹,

Deffit²,

McLetchie³

et al. 2013

Front. Immunol.

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The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.−). This radical is an important precursor of hydrogen peroxide (H2O2) and other reactive oxygen species needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC) crosspresentation by major histocompatibility complex class I molecules through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules.

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Processing and presentation of tetanus toxin by antigen-presenting cells from patients with chronic granulomatous disease (CGD) to human specific T cell clones are not impaired

Cited by 6 publications

References 26 publications

Ex Vivo Monitoring of Antigen-Specific CD4⁺T Cells after Recall Immunization with Tetanus Toxoid

Ex Vivo Monitoring of Antigen-Specific CD4⁺T Cells after Recall Immunization with Tetanus Toxoid

Cutting Edge: NADPH Oxidase Modulates MHC Class II Antigen Presentation by B Cells

A Role for NADPH Oxidase in Antigen Presentation

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Processing and presentation of tetanus toxin by antigen-presenting cells from patients with chronic granulomatous disease (CGD) to human specific T cell clones are not impaired

Cited by 6 publications

References 26 publications

Ex Vivo Monitoring of Antigen-Specific CD4+T Cells after Recall Immunization with Tetanus Toxoid

Ex Vivo Monitoring of Antigen-Specific CD4+T Cells after Recall Immunization with Tetanus Toxoid

Cutting Edge: NADPH Oxidase Modulates MHC Class II Antigen Presentation by B Cells

A Role for NADPH Oxidase in Antigen Presentation

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Ex Vivo Monitoring of Antigen-Specific CD4⁺T Cells after Recall Immunization with Tetanus Toxoid

Ex Vivo Monitoring of Antigen-Specific CD4⁺T Cells after Recall Immunization with Tetanus Toxoid