BACKGROUND: Modified allergen extracts (allergoids) with reduced IgE-binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T-cell stimulatory capacity is less well studied and is a subject of the present study. METHODS: We compared the ability of native house dust mite extract (Dermatophagoides pteronyssinus; HDM) and the glutaraldehyde-modified allergoid (HDM-GA) to induce the proliferation and cytokine production by fresh PBMC and by DC-stimulated polyclonal Th cells and HDM-specific Th cell clones. RESULTS: Freshly isolated T cells showed a partially reduced responsiveness to HDM-GA, differentially pronounced in different donors. HDM-specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM-GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor-dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM-specific T cell clones. CONCLUSIONS: The reduced stimulatory potential of HDM-GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid-nonreactive HDM-specific Th cells may result in differential responses of individual patients to immunotherapy.
BACKGROUND: Modified allergen extracts (allergoids) with reduced IgE-binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T-cell stimulatory capacity is less well studied and is a subject of the present study. METHODS: We compared the ability of native house dust mite extract (Dermatophagoides pteronyssinus; HDM) and the glutaraldehyde-modified allergoid (HDM-GA) to induce the proliferation and cytokine production by fresh PBMC and by DC-stimulated polyclonal Th cells and HDM-specific Th cell clones. RESULTS: Freshly isolated T cells showed a partially reduced responsiveness to HDM-GA, differentially pronounced in different donors. HDM-specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM-GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor-dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM-specific T cell clones. CONCLUSIONS: The reduced stimulatory potential of HDM-GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid-nonreactive HDM-specific Th cells may result in differential responses of individual patients to immunotherapy.
Authors: Bärbel Heydenreich; Iris Bellinghausen; Steffen Lorenz; Helene Henmar; Dennis Strand; Peter A Würtzen; Joachim Saloga Journal: Immunology Date: 2012-06 Impact factor: 7.397
Authors: Alexey V Tkach; Naveena Yanamala; Shyla Stanley; Michael R Shurin; Galina V Shurin; Elena R Kisin; Ashley R Murray; Samantha Pareso; Timur Khaliullin; Gregg P Kotchey; Vincent Castranova; Sanjay Mathur; Bengt Fadeel; Alexander Star; Valerian E Kagan; Anna A Shvedova Journal: Small Date: 2012-08-13 Impact factor: 13.281
Authors: Zoe L Urry; David F Richards; Cheryl Black; Maria Morales; Jerónimo Carnés; Catherine M Hawrylowicz; Douglas S Robinson Journal: BMC Immunol Date: 2014-05-29 Impact factor: 3.615