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Department of Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom
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-
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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