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Background  In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T‐cell response, which was preceded by an early decrease in the frequency of both  IL ‐4+ cells and  sIgE  levels. A progressive increase in  sIgG  4  levels and  FAB  blockage were also found.    Methods  By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow‐up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy.    Results  Thirty patients completed the 5‐year clinical trial protocol. Although individual responses were heterogeneous, reduction in both  sIgE  and circulating  IL ‐4+ cells compared to the initial 1‐ to 4‐month peak was maintained throughout the 3‐year treatment period and for 2 years after discontinuation. Meanwhile, after a 2‐year increase in  sIgG 4, the levels were stabilized during the third year and decreased post‐therapy.  FAB  inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T‐cell response, after  IT  cessation, occurs in two‐thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and  sIgE  titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response.    Conclusion  Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3‐year treatment period) are linked to the acquisition and maintenance of a regulatory T‐cell response.

allergy

Persistent regulatory T‐cell response 2 years after 3 years of grass tablet  SLIT : Links to reduced eosinophil counts,  sIgE  levels, and clinical benefit