Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy.

Background: Allergic sensitization to cat allergens is common and represents a major risk factor for asthma. Specific immunotherapy (SIT) is effective but cumbersome and associated with IgE-dependent adverse events. Immunotherapy targeting allergen-specific T cells, with synthetic peptides representing T-cell epitopes, might improve safety and reduce the duration of treatment.

Production of human T-cell clones.

The study of monoclonal human T-cell populations has had a fundamental impact on our current knowledge of the function, specificity, and mechanisms of activation of these cells. The frequency of antigen-specific T cells in peripheral blood is low, necessitating several enrichment steps prior to the isolation of individual clones. Two different methods of limiting dilution cloning are described in this chapter, the choice of which depends on the availability of starting materials.

Secretion of IFN-gamma and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse.

We report differences in the supramolecular organization of the immunologic synapse (IS) formed by resting and anergic human T cells with agonist peptide-loaded antigen-presenting cells (APCs). T cells reactive to influenza A hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and regulatory by incubation with high doses of agonist peptide in the absence of APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3epsilon and CD3zeta initially accumulate within a ring or arc before redistributing within 30 minutes to single or multiple foci more central to the contact.

T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity.

Background: Synthetic peptides, representing CD4(+) T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils.

Methods And Findings: In this study we address the mechanism of action of peptide immunotherapy (PIT) in cat-allergic, asthmatic patients.

Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios.

Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood.