Generation of Antigen-Specific Suppressor Cells during Allergy Desensitization

Rocklin, Ross E.; Sheffer, Albert L.; Greineder, Dirk K.; Melmon, Kenneth L.

doi:10.1056/nejm198005293022201

Cited by 285 publications

(90 citation statements)

References 29 publications

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“…It has been reported that SIT induces a subpopulation of T cells that can suppress specific antigen-induced T-cell proliferation (45,46). Thus, immunotherapy could act by shifting the balance from T helper toward T suppressor cells, switching off the production of specific IgE.…”

Section: Effect On T Cellsmentioning

confidence: 99%

Mechanisms of specific immunotherapy of allergic diseases

Kowalski

Jutel

1998

Allergy

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Section: Effect On T Cellsmentioning

confidence: 99%

Mechanisms of specific immunotherapy of allergic diseases

Kowalski

Jutel

1998

Allergy

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“…Although complications derived from the impurity of allergens have been overcome by the production of purified recombinant allergens, provocation of possibly life-threatening anaphylaxic reactions remains to be a serious adverse effect. In contrast, immunological mechanisms for the hyposensitization per se have been an issue of much arguments for decades, and a number of mechanisms have been proposed, including generation of blocking Ab, suppressor cells, induction of specific anergy, and clonal deletion (2,3,6,7). Recently, shift of the balance between Th1 and Th2 cell responses has been stressed as the major underlying cause for atopic diseases, in which the Th2 response producing IL-4 predominates over Th1 response producing IFN-␥ resulting in the production of excess IgE Ab (8 -10).…”

mentioning

confidence: 99%

C8/119S Mutation of Major Mite Allergen Derf-2 Leads to Degenerate Secondary Structure and Molecular Polymerization and Induces Potent and Exclusive Th1 Cell Differentiation

Korematsu¹,

Tanaka²,

Hosoi

et al. 2000

The Journal of Immunology

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Hyposensitization therapy for atopic diseases has been conducted for decades but suffered from many problems including anaphylactic reactions. We previously developed a mutant protein of the major mite allergen Derf-2, C8/119S, which showed reduced binding to IgE. The C8/119S mutant was shown to exhibit more efficient hyposensitizing effect than Derf-2 in the animal model of allergic bronchial asthma. In the present study, we indicate that C8/119S exhibits markedly augmented immunogenicity for the proliferation of Derf-2-specific human T cells and T cell clones irrespective of the epitope specificity as compared with Derf-2. Furthermore, C8/119S has induced potent and almost exclusive differentiation of Th1 cells from the peripheral blood of atopic patients in vitro. Neither Ag dosage effect nor absence of B cell-mediated Ag presentation could fully account for these effects. C8/119S has been indicated to lose the characteristic β-barrel structure as judged by circular dichroism spectroscopic analysis and to polymerize solubly in physiological condition. Heating of Derf-2 also caused less stable molecular aggregation, but it hardly affected the secondary structure and failed to induce such a polarity toward the Th1 cell differentiation. These results have indicated that the degenerate secondary structure of C8/119S leading to stable molecular polymerization is primarily responsible for the marked increase in T cell-immunogenicity and the induction of exclusive Th1 cell differentiation in atopic patients. It has been suggested strongly that the recombinant C8/119S protein can provide an effective Ag with the least risk of anaphylaxis for allergen immunotherapy against house dust mite in human.

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“…It has been suggested that selective stimulation of Ts cells or a new formation of antigen-specific Ts cells (20)(21)(22) may be responsible for suppressing IgE synthesis during immunotherapy. In man, isotype-as well as antigen-specific Ts cells have been found in patients treated with immunotherapy, but not in untreated controls (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Mediator release is altered in immunotherapy‐treated patients: a 4‐ear study

Dokic

Nethe

Kleine‐Tebbe

et al. 1996

Allergy

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In recent years, it has been possible to demonstrate mediator release into the nasal secretion after nasal allergen challenge in patients with allergic rhinitis. Using the nasal provocation model, we determined whether the mediator release was altered in immunotherapy-treated patients. Seventeen grass-pollen-allergic patients were examined under controlled, reproducible conditions. Serial challenges with increasing doses of grass pollen produced increasing numbers of clinical symptoms and release of mediators such as kinins, TAME-esterase activity, and histamine. Ten patients received a semidepot perennial grass-pollen extract for 4 years. Seven patients served as controls and did not receive immunotherapy during the observation period. Data from the group of patients receiving immunotherapy over the first year already showed a partially significant decline in the maximal mediator release after nasal allergen challenges compared to the results of pretreated challenges, whereas controls did not show any significant changes. Nasal allergen challenges after termination of 4 years' immunotherapy significantly modified the mediator release compared to pretreatment values (TAME-esterase activity P < 0.05, kinins P < 0.01, and histamine P < 0.01).Decrease of mediator release paralleled the symptom-medication scores and quantitative skin prick test. Finally, we could demonstrate a significant correlation between specific IgG increase and mediator decrease in the treated group.Immunotherapy in patients with pollen allergy has been evaluated by the following criteria: 1) clinical parameters (symptom/medication scores) 2) rhinomanometry (difficult to assess because of 3) direct inquiry, which is highly subjective on the 4) the quantitative skin prick test (QST).Better reproducibility of results was achieved with immunoglobulin measurements (specific IgG and specific IgE), although a statistically significant relation has so far been detectable only between the applied cumulative dose during immunotherapy and the production of IgG antibodies. A direct correlation has not yet been clearly demonstrated between the clinical effectiveness of immunotherapy and IgG antibody production poor reproducibility) part of both the physician and the patient

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Generation of Antigen-Specific Suppressor Cells during Allergy Desensitization

Cited by 285 publications

References 29 publications

Mechanisms of specific immunotherapy of allergic diseases

Mechanisms of specific immunotherapy of allergic diseases

C8/119S Mutation of Major Mite Allergen Derf-2 Leads to Degenerate Secondary Structure and Molecular Polymerization and Induces Potent and Exclusive Th1 Cell Differentiation

Mediator release is altered in immunotherapy‐treated patients: a 4‐ear study

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