Regulation of allergic airway inflammation by adoptive transfer of CD4 + T cells preferentially producing IL-10

• DOI: 10.1016/j.ejphar.2017.06.037
• Publication Date: 2017-06-29T03:15:34Z
• Authors: Masaya Matsuda; Kana Doi; Tatsuya Tsutsumi; Shinya Fujii; Maki Kishima; Kazuma Nishimura; Ikue Kuroda; Yu Tanahashi; Rino Yuasa; Toshihiko Kinjo; Nobuyuki Kuramoto; Nobuaki Mizutani; Takeshi Nabe
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Ovalbumin; Immunoglobulin E; Adoptive Transfer; Asthma; Interleukin-10; 3. Good health; Mice; 03 medical and health sciences; Phenotype; Animals; Cell Proliferation

Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4+ T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-β for 7 days. After the 7-day culture, the CD4+ T cells were purified using a murine CD4 magnetic beads system. When the induced CD4+ T cells were stimulated by OVA in the presence of antigen-presenting cells, IL-10 was preferentially produced in vitro. When CD4+ T cells were adoptively transferred to OVA-sensitized mice followed by intratracheal OVA challenges, IL-10 was preferentially produced in the serum and bronchoalveolar lavage fluid in vivo. IL-10 production coincided with the inhibition of eosinophilic airway inflammation and epithelial mucus plugging. Most of the IL-10-producing CD4+ T cells were negative for Foxp3 and GATA-3, transcription factors of naturally occurring regulatory T cells and Th2 cells, respectively, but double positive for LAG-3 and CD49b, surface markers of inducible regulatory T cells, Tr1 cells. Collectively, most of the induced IL-10-producing CD4+ T cells could be Tr1 cells, which respond to the antigen to produce IL-10, and effectively suppressed allergic airway inflammation. The induced Tr1 cells may be useful for antigen-specific cellular immunotherapy for atopic diseases.