Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects

WLG Oldfield, AB Kay, M Larché - The Journal of Immunology, 2001 - journals.aai.org
WLG Oldfield, AB Kay, M Larché
The Journal of Immunology, 2001journals.aai.org
Allergen-derived peptides can induce T cell tolerance in naive and Ag-primed mice. This is
preceded by transient T cell activation. In humans, intradermal administration of short
allergen-derived T cell peptide epitopes provokes IgE-independent isolated late asthmatic
reactions (LARs) in sensitized subjects. In this study, we determine whether, as in mouse
models, such peptides produce hyporesponsiveness to rechallenge with peptides, or whole
allergen, either clinically or in terms of in vitro T cell responses. We found that a second …
Abstract
Allergen-derived peptides can induce T cell tolerance in naive and Ag-primed mice. This is preceded by transient T cell activation. In humans, intradermal administration of short allergen-derived T cell peptide epitopes provokes IgE-independent isolated late asthmatic reactions (LARs) in sensitized subjects. In this study, we determine whether, as in mouse models, such peptides produce hyporesponsiveness to rechallenge with peptides, or whole allergen, either clinically or in terms of in vitro T cell responses. We found that a second injection of cat allergen (Fel d 1)-derived T cell peptides was associated with a marked reduction, or absence, of the LAR, and that up to 40 wk was required for return to baseline values. The cutaneous late-phase reaction to whole cat dander was also inhibited, even in subjects who did not experience an initial LAR. These observations were associated with a significant decrease in peptide-and whole allergen-induced proliferation of PBMCs and the production of IL-4, IL-13, and IFN-γ in cultures. Thus, allergen-derived peptides induce tolerance to subsequent peptide injection in the target organ (the lung), reduce late-phase cutaneous responsiveness to whole allergen, and alter in vitro T cell reactivity.
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