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Analysis of the CD4+ T cell responses to house dust mite allergoid
P Kalinski1, M C Lebre, D Kramer
1Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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.