Peptide therapy for allergic diseases:: basic mechanisms and new clinical approaches

被引:21
作者
Larché, M [1 ]
机构
[1] Univ London Imperial Coll Sci & Technol, Dept Allergy & Clin Immunol, Fac Med, Natl Heart & Lung Inst, London SW3 6LY, England
基金
英国医学研究理事会;
关键词
asthma; epitope; immunological tolerance; immunology; major histocompatibility complex;
D O I
10.1016/j.pharmthera.2005.05.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Desensitising allergen immunotherapy has been practised for many decades, Although time consuming, this form of therapy is antigen-specific and disease-modifying, in contrast to palliative pharmacotherapy. However, the use of allergen extracts containing native allergen molecules frequently results in allergic adverse reactions to treatment. Several strategies to reduce the allergenicity of therapeutic preparations, while maintaining their therapeutic benefit, are being developed. Peptide inununotherapy is one such approach. Short synthetic peptides, comprising T cell epitopes of major allergens, were unable to crosslink allergen-specific IgE molecules oil basophils in vitro. Treatment of allergic volunteers with allergen peptides resulted in reduced skin, lung and nasal sensitivity to allergen challenge and improved their Subjective ability to tolerate allergen exposure. Peptides reduced pro-inflammatory cytokine secretion from peripheral blood cells, whilst increasing the immunosuppressive cytokine IL-10. Furthermore, peptide therapy was associated with the induction of a Population of CD4+ T cells with a Suppressive functional phenotype. Thus, peptide therapy may be Suitable for the antigen-specific treatment of allergic diseases. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:353 / 361
页数:9
相关论文
共 69 条
[1]   Epitope-specific T cell tolerance to phospholipase A(2) in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro [J].
Akdis, CA ;
Akdis, M ;
Blesken, T ;
Wymann, D ;
Alkan, SS ;
Muller, U ;
Blaser, K .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (07) :1676-1683
[2]   Role of IL-10 in allergen-specific immunotherapy and normal response to allergens [J].
Akdis, CA ;
Blaser, K .
MICROBES AND INFECTION, 2001, 3 (11) :891-898
[3]   Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells [J].
Akdis, M ;
Verhagen, J ;
Taylor, A ;
Karamloo, F ;
Karagiannidis, C ;
Crameri, R ;
Thunberg, S ;
Deniz, G ;
Valenta, R ;
Fiebig, H ;
Kegel, C ;
Disch, R ;
Schmidt-Weber, CB ;
Blaser, K ;
Akdis, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (11) :1567-1575
[4]   Fel d 1-derived T cell peptide therapy induces recruitment of CD4+CD25+;: CD4+ interferon-γ+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects [J].
Alexander, C ;
Ying, S ;
Kay, AB ;
Larché, M .
CLINICAL AND EXPERIMENTAL ALLERGY, 2005, 35 (01) :52-58
[5]  
Alexander C, 2001, J ALLERGY CLIN IMMUN, V107, pS217
[6]   Late asthmatic reactions induced by inhalation of allergen-derived T cell peptides [J].
Ali, FR ;
Oldfield, WLG ;
Higashi, N ;
Larché, M ;
Kay, AB .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (01) :20-26
[7]   ACTIVATION OF T-CELLS RECOGNIZING SELF 60-KD HEAT-SHOCK PROTEIN CAN PROTECT AGAINST EXPERIMENTAL ARTHRITIS [J].
ANDERTON, SM ;
VANDERZEE, R ;
PRAKKEN, B ;
NOORDZIJ, A ;
VANEDEN, W .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (03) :943-952
[8]  
Anderton SM, 1998, CIBA F SYMP, V215, P120
[9]   Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice [J].
Astori, M ;
von Garnier, C ;
Kettner, A ;
Dufour, N ;
Corradin, G ;
Spertini, F .
JOURNAL OF IMMUNOLOGY, 2000, 165 (06) :3497-3505
[10]   Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1 [J].
Bauer, L ;
Bohle, B ;
JahnSchmid, B ;
Wiedermann, U ;
Daser, A ;
Renz, H ;
Kraft, D ;
Ebner, C .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 1997, 107 (03) :536-541