Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats

doi:10.1016/S0091-6749(98)70294-5

Journal of Allergy and Clinical Immunology

Volume 102, Issue 4, October 1998, Pages 571-578

https://doi.org/10.1016/S0091-6749(98)70294-5 Get rights and content

Abstract

Background: Cells producing a T_h2 -cytokine profile play an important role in the onset and maintenance of atopic diseases, and therefore specific immunotherapy is aimed to induce a switch to cells producing a T_h1 - or T_h0 -cytokine profile. Recently, a novel form of immunotherapy making use of synthetic peptides from the major cat allergen Fel d 1 has been developed, but its mechanisms of action are unknown. Objectives: We examined the effects of immunotherapy with Fel d 1 peptides on the response to bronchial provocation tests (PD₂₀ FEV₁ ) with a standardized Fel d 1 cat extract on Fel d 1–specific serum IgE and IgG levels and in vitro IL-4 and IFN-γ production. Methods: Patients allergic to cats received 6 weekly injections of 7.5 μg (low dose), 75 μg (medium dose), or 750 μg (high dose) of Fel d 1 peptides (25 patients) or a placebo (6 patients). Results: Six weeks after ending immunotherapy, posttreatment PD₂₀ FEV₁ was not significantly different between the treated and placebo groups. However, in the medium- and high-dose groups there was a significant improvement between baseline and posttreatment days. IL-4 release was significantly reduced in the high dose–treated group (P < .005, Wilcoxon W test), whereas it was unchanged in the low or medium dose– and in the placebo-treated groups. In all groups, IFN-γ, IgE, and IgG levels remained unchanged. Conclusion: There was no correlation between the improvement of PD₂₀ FEV₁ and the decrease in IL-4 production. These data suggest that peptide immunotherapy may act by shifting the Fel d 1–induced response of PBMCs in vitro from the T_h2 -like to the T_h0 -like phenotype. (J Allergy Clin Immunol 1998;102:571-8.)

Section snippets

Patients

Nineteen men and 12 women, ranging in age from 20 to 37 years (mean ± SD: 27.7 ± 5.1 years), were recruited in the Allergy Department of the Montpellier Hospital on the basis of a clinical history of allergy to cats and enrolled in the present double-blind, placebo-controlled study of cytokine release by PBMC in vitro. All patients were first seen with (1) a positive skin prick test response performed as previously described²⁰ to the Aquagen extract, (2) a positive bronchial challenge to the

Clinical efficacy of peptide immunotherapy

PD₂₀ FEV₁ varied widely between the different groups of patients. As shown in Fig 1, 6 weeks after ending immunotherapy, posttreatment PD₂₀ FEV₁ was not significantly different between the treated and placebo groups.

. Effect of Fel d 1 peptides on cat allergen PD₂₀ FEV₁ . Patients were divided into 4 groups according to the treatment they received as indicated in Methods section. Bronchial challenge of patients was performed as described in Methods section before (baseline) and after the

DISCUSSION

The results presented in this study show that immunotherapy with Fel d 1 peptides (ALLERVAX CAT) of individuals allergic to cats results in an increase of PD₂₀ FEV₁ and is accompanied by a suppression of the in vitro IL-4 release by PBMCs stimulated with a cat allergen extract, whereas the production of IFN-γ was not affected. These data suggest that peptide immunotherapy of allergic patients may be acting by altering the cytokine profile of the in vitro cat allergen–induced response of PBMCs

Acknowledgements

We thank Drs François Rousset and Jacques Banchereau for providing the mAbs anti-IFN-γ, and Dr Alison Campbell for revising the manuscript.

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Treatment with grass allergen peptides led to an improvement in allergic rhinoconjunctivitis symptoms after 3 intervening GPSs, corresponding to up to 2 years off treatment.
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We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides.
A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen–induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed.
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^☆: From ^a the INSERM U. 454 and ^b the Clinique des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier; and ^c ImmuLogic, Waltham.

^☆☆: Supported by Hoechst Marion Roussel, Kansas City, Mo.

^★: Reprint requests: Jérôme Pène, PhD, INSERM U.454, Hôpital Arnaud de Villeneuve, 375, avenue du Doyen G. Giraud, 34295 Montpellier cedex 5, France.

^★★: 0091-6749/98 $5.00 + 0 1/1/92394

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Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats☆,☆☆,★,★★

Abstract

Section snippets

Patients

Clinical efficacy of peptide immunotherapy

DISCUSSION

Acknowledgements

Immunol Today

Immunol Today

J Allergy Clin Immunol

Mol Immunol

J Allergy Clin Immunol

Immunopharmacology

Eur J Pharmacol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties

Annu Rev Immunol

Lymphokine production by human T cells in disease states

Annu Rev Immunol

IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons γ and α and prostaglandin E2

Proc Natl Acad Sci USA

IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-γ

J Immunol

IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants

J Immunol

Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens

J Exp Med

Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signaling pathways

J Immunol

Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma

N Engl J Med

Differences in IL-4 release by PBMC are related with heterogeneity of atopy

Immunology