The immune checkpoint molecule VISTA regulates allergen-specific Th2-mediated immune responses

• Published in: International immunology 2018-02, Vol.30 (1), p.3-11
• Main Authors: Ohno, Tatsukuni, Zhang, Chenyang, Kondo, Yuta, Kang, Siwen, Furusawa, Emi, Tsuchiya, Kimitake, Miyazaki, Yasunari, Azuma, Miyuki
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antigen-Antibody Reactions; Asthma - drug therapy; Asthma - immunology; Bronchial Hyperreactivity - immunology; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - immunology; CD4-Positive T-Lymphocytes - immunology; Disease Models, Animal; Eosinophils - immunology; Female; Flow Cytometry; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Ovalbumin - immunology; Th2 Cells - cytology; Th2 Cells - immunology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxx070

VISTA inhibits allergic inflammation in asthma Abstract V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel immune checkpoint receptor and ligand that regulates T-cell activation. We investigated the functional involvement of VISTA in Th2 cell-mediated immune responses using an ovalbumin (OVA)-induced allergic asthma model. Treatment with an anti-VISTA monoclonal antibody (mAb) during allergen sensitization increased the production of antibodies, including total IgE, OVA-specific IgG1 and IgG2a and allergen-specific IL-5 and IL-13; it also increased the expression of IL-13 by splenic CD4+ T cells. However, treatment with the anti-VISTA mAb during sensitization did not accelerate asthmatic responses, including airway hyper-responsiveness (AHR) or the number of eosinophils in bronchoalveolar lavage (BAL) fluid. In contrast, treatment with the anti-VISTA mAb during allergen challenge significantly augmented AHR and BAL fluid eosinophilia. This treatment also increased the production of IL-5 and IL-13 in BAL fluid and the expression of IL-13 by CD4+ T cells in draining lymph nodes. These results suggest that VISTA is involved in the regulation of Th2 cell generation and Th2 cell-mediated antibody production and regulates asthmatic responses, especially in the effector phase.