Background: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. Objective: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients. Methods: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG 1-and IgG 4-switched Der p 1-specific B cells, plasmablasts, and IL-10and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. Results: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 6 0.28 to 2.45 6 0.24 (P 5 .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 6 1.3 to 2.7 6 0.5 mm (P 5 .001). IgG 4 1 and IgA 1 Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG 4 1 but not the IgA 1 fraction. The frequency of plasmablasts and IL-10-and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4 1 B cells, plasmablasts, and IL-10 1 and dual-positive IL-10 1 IL-1RA 1 Breg cells significantly correlated with improved clinical symptoms over the course of AIT. Conclusion: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA-and IgG 4expressing Der p 1-specific B cells, plasmablasts, and IL-10 1 and/or IL-1RA 1 Breg cells.
Background: Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells.
Methods:We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30 weeks, and 3 years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramerpositive cells and correlated with nasal symptom score.
Results: Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3 + Helios + CD25 + CD127 − Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3) + CD25 + Treg cells decreased substantially from baseline after 3 years of AIT. ILT3 + Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30 weeks, but only IL-10 + Der p 1-specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3 + Helios + and IL-10 + and decreased ILT3 + Treg cell responses correlated with improved allergic symptoms. Conclusion: The results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.
K E Y W O R D Sallergen-specific T cells, antigen-specific immunotherapy, house dust mite allergy, Treg Abbreviations: AIT, antigen-specific immunotherapy; AR, allergic rhinitis; HDM, house dust mite; ILT3, immunoglobulin-like transcript 3; Treg, T regulatory.
Eighty-seven high-risk individuals in Thailand who had received a complete course of recombinant HBV vaccine 18-20 y ago were investigated with regard to their immunological memory. To evaluate humoral immunity, anti-HBs antibody titers were measured. Cellular immunity was determined by ELISPOT to detect HBV-specific IFN-gamma-producing cells. Overall 83.9% of participants developed circulating anti-HBs (titer > or = 1 mIU/mL) and 58.6% were seroprotected (titer > or = 10 mIU/mL). As for cellular immunity, 50.6% were positive on ELISPOT. Moreover, there was no correlation between the level of anti-HBs and positive ELISPOT results. However, the majority of participants (81.8%) who were positive for IFN-gamma-producing cells were seropositive, but only 50% of seropositive participants were ELISPOT-positive. Thus, 18-20 y after immunization, it appears that a second booster dose should be considered, especially in high-risk groups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.