title: Responses of CD4(+) CD25(+) Foxp3(+)  and IL-10-secreting type I T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children.
abstract: We investigated the effects of cluster specific immunotherapy (SIT) with Dermatophagoides pteronyssinus (Der p) on CD4(+) CD25(+) Foxp3(+) Treg cells and IL-10-secreting type I T regulatory (Tr1) cells in Der p-sensitized children with allergic rhinitis (AR). We performed a prospective randomized study involving 46 children (aged 8-13 yr), of whom 25 children received Der p-SIT + pharmacotherapy and 21 received only pharmacotherapy, over a period of 1 yr. Prior to and at end of treatment, CD4(+) CD25(+) Foxp3(+) Treg cells and allergen-specific IL-10(+) IL-4(-) , IFN-γ(+) IL-4(-) , and IL-4(+) IFN-γ-CD4(+) T cells were measured by flow cytometry. Similarly, IL-4, IFN-γ, and IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell (PBMC) cultures were measured by ELISA, and the suppressive effect of CD4(+) CD25(high) T cells on cell proliferation and cytokine release was estimated from both groups. Allergen-specific serum IgE and IgG4 were also assessed at the beginning and end of treatment by RAST and ELISA, respectively. The levels of allergen-specific Tr1 cells, IgG4, and allergen-induced IL-10 synthesis from PBMC cultures were significantly increased after SIT for 1 yr compared with baseline levels (p < 0.001 for all), with significant correlation between increased levels of Tr1 cells and improvements in nasal symptoms (r = 0.48, p < 0.05). In contrast, the levels of CD4(+) CD25(+) Foxp3(+) T cells, allergen-specific Th1 and Th2 cells, the production of IL-4 and IFN-γ, and the function of CD4(+) CD25(high) T cells were not altered in either group at the end of treatment. These data suggest that the up-regulation of Tr1 cells may play an important role in SIT and be a useful marker of successful SIT in AR patients.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lou
authors.forename: Chengshuo
authors.initials: C
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Demin
authors.initials: D
authors.lastname: Han
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D060829:Arthropod Proteins / Q000276:immunology / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology; D002469:Cell Separation; D002648:Child; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D060829:Arthropod Proteins; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10