Analysis of the CD4+ T cell responses to house dust mite allergoid.
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.
Kalinski
P
P
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Lebre
M C
MC
Kramer
D
D
De Jong
E C
EC
Van Schijndel
J W P M
JW
Kapsenberg
M L
ML
D000485:Allergens / Q000276:immunology; D000080384:Allergoids; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D010936:Plant Extracts / Q000276:immunology*
D000485:Allergens; D000080384:Allergoids; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010936:Plant Extracts