Material Supplementary 9.DC1 http://www.jimmunol.org/content/suppl/2010/01/04/jimmunol.090137 Subscription http://jimmunol.org/subscription is online at: The Journal of Immunology Information about subscribing to Permissions Correction of an imbalance between allergen-specific T cell subsets is considered a critical event in establishing allergen tolerance by specific immunotherapy (SIT). In a comprehensive, longitudinal study, distinct T cell populations and Ig subtypes were analyzed in

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... s allergic to birch pollen during decisive time points of SIT (i.e., induction and maintenance phase), as well as in and out of birch pollen season. An increase in Bet v 1-specific, IL-10-secreting T cells, fulfilling the criteria of inducible type 1 regulatory T (Tr1) cells, was observed by the end of the induction phase; this resulted in a decreased ratio of allergen-specific IL-5 + Th2/Tr1 cells. In contrast, CD4 + CD25 + CD127 low regulatory T cell numbers did not change. Furthermore, enhanced concentrations of allergen-specific IgG Abs were observed, whereas allergen-specific IgE and IgA levels remained unchanged. After 1 y of SIT, a reduced ratio of allergen-specific Th2/IFN-g + Th1 cells was apparent. Although untreated and SIT-treated allergic subjects developed enhanced Th2 cell responses during birch pollen season, only SIT-treated patients experienced elevated numbers of allergen-specific Tr1 cells, which were associated with reduced skin prick test reactivity and diminished clinical symptoms. In coculture assays, allergen-specific Tr1 cells showed an IL-10-and dose-dependent inhibition of CD4 + CD25 2 T effector cells. Thus, SIT has differential effects on regulatory T cell subsets, resulting in an early induction of allergen-specific Tr1 cells associated with an increase in allergen-specific IgG, and it leads to a delayed shift from an allergen-specific Th2-to a Th1-dominated immune response. FIGURE 6. SIT results in increased serum concentrations of allergen-specific IgG Abs. Birch pollen-specific IgE (A), IgA (B), IgG (C), and IgG4 (D) Ab concentrations before (m0) and during the first 12 mo (m12) of SIT. Ratio of allergen-specific IgE/IgG (E) and IgE/IgG4 (F) over the 12-mo observation period.