Regulatory T and B cells in peripheral blood of subcutaneous immunotherapy-treated Japanese cedar pollinosis patients.

AIM: The aim of this study was to clarify whether there are more regulatory T (Treg) and regulatory B (Breg) cells, and higher levels of IL-10-related transcription factors in subcutaneous immunotherapy (SCIT)-treated pollinosis patients than in non-SCIT-treated patients. METHODS: Japanese cedar pollinosis patients undergoing SCIT had received treatment for at least 2.8 years. Peripheral blood mononuclear cells were used for flow cytometer analyses and mRNA measurement. RESULTS: The numbers of type 1 regulatory T (Tr1)-like cells and Breg cells, and expression of E4BP4 mRNA by peripheral blood mononuclear cells in SCIT-treated patients were higher than those in non-SCIT-treated patients. CONCLUSION: Tr1-like cells, Breg cells and E4BP4 may be involved in the effectiveness of SCIT.

Phenotype analyses of IL-10-producing Foxp3- CD4+ T cells increased by subcutaneous immunotherapy in allergic airway inflammation.

INTRODUCTION: The mechanisms of allergen immunotherapy are not fully elucidated. Here, we sought to develop a murine model to demonstrate the effectiveness of subcutaneous immunotherapy (SCIT) for allergic responses. As excessive antigen dosages may induce immune tolerance in sensitized mice, the effects of SCIT were assessed by varying the antigen dosage. The mechanisms of SCIT were analyzed by focusing on the induction of Foxp3+ Treg cells and IL-10-producing Foxp3- CD4+ T cells, as well as on the phenotype of the latter cells. METHODS: Ovalbumin (OVA) + Al(OH)3-sensitized mice received subcutaneous dosages of OVA at 0.01, 0.1 or 1 mg/animal for SCIT, followed by intratracheal challenges with OVA at 5, 50 or 500 µg/animal. RESULTS: The maximum effects of SCIT were observed with 1 mg/animal of OVA for airway inflammation induced by 5 µg/animal of OVA, in which airway eosinophilia and Th2 cytokine production were markedly suppressed. The increase in the OVA-specific IgE level was significantly suppressed by SCIT. The development of bronchial epithelial thickening and mucus accumulation were also suppressed by SCIT. Concomitantly, IL-10-producing Foxp3- CD4+ T cells were increased in the lungs by SCIT, but Foxp3+ Treg cells were not. Most of the induced IL-10-producing Foxp3- CD4+ T cells were negative for either IL-5 or LAG-3, but positive for CD49b. CONCLUSION: We successfully developed an airway allergic model for SCIT. It was suggested that most of IL-10-producing Foxp3- CD4+ regulatory T cells increased by SCIT in the lungs were CD49b+ CD4+ regulatory T cells, but neither Th2 cells nor Tr1 cells.