Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Overtvelt, Laurence Van; Wambre, Erik; Maillère, Bernard; Hofe, Eric von; Louise, Anne; Balazuc, Anne-Marie; Bohle, Barbara; Ebo, Didier G.; Leboulaire, Christophe; Garcia, Gilles; Moingeon, Philippe

doi:10.4049/jimmunol.180.7.4514

Cited by 111 publications

(138 citation statements)

References 57 publications

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“…Allergen may not be the only stimulus. The observed 66.3% increase in Unc119 expression in CD4 T cell population is unlikely to have its roots solely in allergen-specific T cells, which are rare and account for 0.0001-0.1% of the total T cell population (45). Thus, other stimuli (e.g., cytokines) are likely to affect the Unc119 level.…”

Section: Discussionmentioning

confidence: 99%

Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma

Górska

Goplen²,

Qiang³

et al. 2010

The Journal of Immunology

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The Th2 bias is a hallmark of allergic diseases. In this study, we show that the Th1 versus Th2 balance and the development of allergic asthma are strongly affected by the signaling protein uncoordinated 119 (Unc119). The expression of this adaptor protein is significantly increased in Th2 cells. Unc119 activates the Src family and inhibits the Abl family of tyrosine kinases. The activated Src family kinase Lck stimulates the activity of Itk and the expression of the transcription factor JunB. As a result, Unc119 promotes IL-4 production. Through inhibition of Abl kinases, Unc119 dampens IFN-γ production. Using adoptive transfer of Unc119-knockdown CD4 T cells, we show a critical role for Unc119 in the development of eosinophilic inflammation of airways, mucus production, and bronchial hyperreactivity in a mouse model. Intriguingly, the expression of the Unc119 protein is enhanced in CD4 T cells from patients with asthma. We speculate that the heightened expression of Unc119 promotes Th2, inhibits Th1 differentiation, and contributes to the pathogenesis of asthma in humans.

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Section: Discussionmentioning

confidence: 99%

Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma

Górska

Goplen²,

Qiang³

et al. 2010

The Journal of Immunology

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“…The timing of allergen exposure could plausibly be anticipated to influence a patient's allergen-reactive T-cell pool. Indeed, increased frequency of pollen-specific CD4 + T cells has been described during pollen season whereas such fluctuation does not occur for the perennial allergen house dust mite (29)(30)(31). Furthermore, a greater frequency of birch-pollen reactive CD4 + Tem has been shown in the blood of pollen allergic individuals during pollen season, compared with a greater percentage of Tcm in house dust mite allergic patients (29).…”

Section: Discussionmentioning

confidence: 99%

“…Antigen-experienced T cells can be phenotypically classified into effector and memory T-cell populations, the latter being subdivided into effector memory T cells (Tem) and central memory T cells (Tcm) (27,28). Importantly, the phenotype and frequency of allergen-reactive T cells can vary, depending on the presence or absence of allergen exposure (e.g., perennial vs. seasonal allergy) (29)(30)(31). In addition, the phenotype of T cells in the end organ (e.g., the lung) may differ from those in peripheral blood (32)(33)(34).…”

mentioning

confidence: 99%

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mackenzie

Nowakowska

Leech

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergenexperienced T cells. CD62L expression by allergen-experienced T cells corresponds to effector/effector memory (CD62L lo ) and central memory (CD62L hi ) subsets, which vary with allergen exposure (e.g., during, or out with, pollen season). The efficacy of PIT on different T helper 2 (Th2) cell memory populations is unknown. We developed a murine model of PIT in allergic airway inflammation (AAI) driven by adoptively transferred, traceable ovalbumin-experienced Th2 cells. PIT effectively suppressed AAI driven by unfractionated Th2 cells. Selective transfer of CD62L hi and CD62L lo Th2 cells revealed that these two populations behaved differently from one another and from previously characterized (early deletional) responses of naive CD4 + T cells to PIT. Most notably, allergen-reactive CD62L lo Th2 cells were long-lived within the lung after PIT, before allergen challenge, in contrast to CD62L hi Th2 cells. Despite this, PIT was most potent against CD62L lo Th2 cells in protecting from AAI, impairing their ability to produce Th2 cytokines, whereas this capacity was heightened in PIT-treated CD62L hi Th2 cells. We conclude that Th2 cells do not undergo an early deletional form of tolerance after PIT. Moreover, memory Th2 subsets respond differently to PIT. These findings have implications for the clinical translation of PIT in different allergic scenarios.

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“…3). Cytokine expression was strictly Ag dependent, as no significant numbers of cytokine-positive cells were detectable when aAPCs used for coculture experiments presented the noncognate Bet v 1 [4][5][6][7][8][9][10][11][12][13][14][15] peptide in the presence of CD80 (Fig. 9B).…”

Section: Similar Results Were Obtained With An Art V 1-specific Tcr Imentioning

confidence: 99%

“…This region is located at the highly conserved C terminus of Bet v 1 and shares considerable homology with related food and pollen allergens (3). Recent studies have demonstrated that various Bet v 1 peptides bind with high affinity to different HLA-DR molecules (4). The structures targeted by both the humoral and cellular immune responses to Bet v 1 are sufficiently characterized at the molecular level to allow the development of knowledge-based therapies for treatment of birch pollen atopic disorders (3,5).…”

mentioning

confidence: 99%

Human TCR Transgenic Bet v 1-Specific Th1 Cells Suppress the Effector Function of Bet v 1-Specific Th2 Cells

Neunkirchner

Reichl

Schmetterer

et al. 2011

The Journal of Immunology

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Pollinosis to birch pollen is a common type I allergy in the Northern Hemisphere. Moreover, birch pollen-allergic individuals sensitized to the major birch pollen allergen Bet v 1 frequently develop allergic reactions to stone fruits, hazelnuts, and certain vegetables due to immunological cross-reactivity. The major T cell epitope Bet v 1142–153 plays an important role in cross-reactivity between the respiratory allergen Bet v 1 and its homologous food allergens. In this study, we cloned and functionally analyzed a human αβ TCR specific for the immunodominant epitope Bet v 1142–153. cDNAs encoding TCR α- and β-chains were amplified from a Bet v 1142–153-specific T cell clone, introduced into Jurkat T cells and peripheral blood T lymphocytes of allergic and nonallergic individuals, and evaluated functionally. The resulting TCR transgenic (TCRtg) T cells responded in an allergen-specific and costimulation-dependent manner to APCs either pulsed with Bet v 1142–153 peptide or coexpressing invariant chain::Bet v 1142–153 fusion proteins. TCRtg T cells responded to Bet v 1-related food and tree pollen allergens that were processed and presented by monocyte-derived dendritic cells. Bet v 1142–153-presenting but not Bet v 14–15-presenting artificial APCs coexpressing membrane-bound IL-12 polarized allergen-specific TCRtg T cells toward a Th1 phenotype, producing high levels of IFN-γ. Coculture of such Th1-polarized T cells with allergen-specific Th2-differentiated T cells significantly suppressed Th2 effector cytokine production. These data suggest that human allergen-specific TCR can transfer the fine specificity of the original T cell clone to heterologous T cells, which in turn can be instructed to modulate the effector function of the disease initiating/perpetuating allergen-specific Th2-differentiated T cells.

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Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Cited by 111 publications

References 57 publications

Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma

Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Human TCR Transgenic Bet v 1-Specific Th1 Cells Suppress the Effector Function of Bet v 1-Specific Th2 Cells

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