Sublingual administration of Phleum pratense allergen immunotherapy (SLIT) tablets is a clinically efficient treatment for grass pollen–induced rhinoconjunctivitis. This immunotherapy downregulates T_H2 immune responses, induces tolerogenic pathways, and increases regulatory T cells. However, associated immune response markers of allergen desensitization remain undefined.

We sought to characterize the kinetics of individual changes in the immunologic response to grass tablet SLIT.

We evaluated the systemic effects of SLIT in a longitudinal analysis of humoral and cellular immune parameters in peripheral blood samples.

Grass tablet SLIT administration induced a 2-phase systemic humoral and cellular response. The T_H2 response was initially exacerbated and detected as increased allergen-specific IgE (sIgE) and IgG₄ (sIgG₄) levels and an increase in IL-4–producing cells, followed by downregulation of the T_H2 response with a shift toward a T_H1 cytokine profile. T cells with a regulatory phenotype were also elicited. Statistical correlations between immunologic measurements for each patient throughout therapy indicated that T_H2 response downregulation and reduction of the immediate SLIT-induced IgE response were associated with increased allergen-specific IgG₄ synthesis early in therapy. T_H2 response downregulation by month 4 correlated with increased frequency of CD4⁺ T cells with a regulatory phenotype by 12 months.

Changes in sIgE levels after therapy were linked to a specific IgG₄ response, and production of blocking antibodies correlated with T_H2 response downregulation. Reduced IL-4⁺ cell frequency was linked to an increase in the frequency of CD4⁺ T cells with a regulatory phenotype. Changes in sIgE levels and reduced IL-4 and blocking antibody levels could thus be used as indicators of a patient's immune response to therapy.