Immune Regulation by CD4+CD25+ Regulatory T Cells in Patients with Japanese Cedar Pollinosis

Background: Evidence indicating that CD4+CD25+ regulatory T (Treg) cells play a crucial role in the maintenance of peripheral T cell tolerance to allergens has been accumulated. To explore the functional role of Treg cells in patients with Japanese cedar pollinosis, we performed an in vitro investigation of the regulation of immune responses to allergens by Treg cells. Methods: CD4+ and CD4+CD25– T cells obtained from 12 patients with Japanese cedar pollinosis were stimulated with Cry j 1 protein and Cry j 1-derived peptide. On day 6, T cells were tested for allergen-specific reactivity using a CFSE-based proliferation assay and cytokine ELISA assays. The frequency of Cry j 1-specific interleukin (IL)-10-producing Treg cells was assessed by ELISPOT assays. Results: The proportion of proliferated cells induced by allergen stimulation was similar in both CD4+ and CD4+CD25– cell cultures. The production of interferon (IFN)-γ, but not that of IL-5 was significantly enhanced in CD4+CD25– cell cultures compared to that in CD4+ cell cultures. Interestingly, the production of IL-10 was decreased in CD4+CD25– cell cultures. Moreover, Cry j 1-specific IL-10-producing Treg cells were detected in pollen-allergic patients. Conclusion: Our findings suggest that in pollen-allergic patients, Treg cells predominantly suppresses Th1 responses rather than Th2 responses, where allergen-specific IL-10-producing Treg cells may also be responsible for the downregulation of allergen-specific immune responses.