Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation.
BACKGROUND
Sublingual administration of Phleum pratense allergen immunotherapy (SLIT) tablets is a clinically efficient treatment for grass pollen-induced rhinoconjunctivitis. This immunotherapy downregulates TH2 immune responses, induces tolerogenic pathways, and increases regulatory T cells. However, associated immune response markers of allergen desensitization remain undefined.


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


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


RESULTS
Grass tablet SLIT administration induced a 2-phase systemic humoral and cellular response. The TH2 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 TH2 response with a shift toward a TH1 cytokine profile. T cells with a regulatory phenotype were also elicited. Statistical correlations between immunologic measurements for each patient throughout therapy indicated that TH2 response downregulation and reduction of the immediate SLIT-induced IgE response were associated with increased allergen-specific IgG4 synthesis early in therapy. TH2 response downregulation by month 4 correlated with increased frequency of CD4(+) T cells with a regulatory phenotype by 12 months.


CONCLUSION
Changes in sIgE levels after therapy were linked to a specific IgG4 response, and production of blocking antibodies correlated with TH2 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.
['Suárez-Fueyo|Abel|A|', 'Ramos|Tania|T|', 'Galán|Agustín|A|', 'Jimeno|Lucia|L|', 'Wurtzen|Peter A|PA|', 'Marin|Alicia|A|', 'de Frutos|Consolación|C|', 'Blanco|Carlos|C|', 'Carrera|Ana C|AC|', 'Barber|Domingo|D|', 'Varona|Rosa|R|']
D000328:Adult D005786:Gene Expression Regulation D006801:Humans D056724:Immunity, Humoral D007073:Immunoglobulin E D007074:Immunoglobulin G D056747:Immunomodulation D015847:Interleukin-4 D031784:Phleum D010936:Plant Extracts D006255:Rhinitis, Allergic, Seasonal D063729:Sublingual Immunotherapy D050378:T-Lymphocytes, Regulatory D013607:Tablets D018417:Th1 Cells D018418:Th2 Cells
Sublingual immunotherapy SLIT Regulatory T regulatory T cells Allergen-specific IgE IgE sIgE IL-4 Allergen-specific IgG CTLA-4 Cytotoxic T lymphocyte–associated antigen 4 GPS Grass pollen season IgE-FAB IgE-facilitated antigen binding IgG(4) Induced regulatory T Treg allergic rhinitis iTreg sIgG