Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with the allergen-specific modulation of immune reactivity.

Background Timothy grass (TG) pollen is a common seasonal airborne allergen associated with symptoms ranging from mild rhinitis to severe asthma. Objective The aim of this study was to characterize changes in TG-specific T cell responses as a function of seasonality. Methods Peripheral blood mononuclear cells (PBMC) obtained from allergic individuals and non-allergic controls, either during the pollen season or out-of-season, were stimulated either with TG extract or a pool of previously identified immunodominant antigenic regions. Results PBMC from allergic subjects exhibit higher IL-5 and IL-10 responses in-season than when collected out of season. In the case of non-allergic subjects, as expected we observed lower IL-5 responses and robust production of IFNγ compared to allergic individuals. Strikingly, non-allergic donors exhibited an opposing pattern, with decreased immune reactivity in-season. The broad downregulation in non-allergic donors indicates that healthy individuals are not oblivious to allergen exposure but rather react with an active modulation of responses following the antigenic stimulus provided during the pollen season. Transcriptomic analysis of allergen-specific T cells defined genes modulated in concomitance with allergen exposure and inhibition of responses in non-allergic donors. Conclusion and Clinical Relevance Magnitude and functionality of T-helper cell responses differ substantially in-season versus out-of-season in allergic and non-allergic subjects. The results indicate specific and opposing modulation of immune responses following the antigenic stimulation during the pollen season. This seasonal modulation reflects the enactment of specific molecular programs associated with health and allergic disease. This article is protected by copyright. All rights reserved.