Anti-T-cell strategies in the treatment of allergic disease


Mark Larché
Department of Allergy & Clinical Immunology
Imperial College School of Medicine
National Heart & Lung Institute
London SW3 6LY


Specific allergen immunotherapy (SIT) has been shown to be effective in modulating allergic responses in diseases such as rhinitis and asthma. However, the ability of whole allergen to cross link mast cell bound IgE, resulting in release of mediators such as histamine, has limited the application of this therapy to carefully selected patients who have failed conventional pharmacotherapy. The use of peptide sequences corresponding to T cell epitopes of the allergen has been postulated as an alternative to SIT in which high molar doses of T cell epitope can be delivered over a shorter time period and with improved safety. Using peptides from the sequence of the major cat allergen, Fel d 1, we have demonstrated the ability to induce transient T cell activation, resulting in isolated late asthmatic reactions, which are followed by prolonged periods of allergen-specific hyporesponsiveness, both to peptide re-challenge and to cutaneous challenge with whole allergen. Thus, peptide therapy may prove safe and efficacious in the treatment of allergic diseases.