title: Expanding regulatory T cells alleviates chikungunya virus-induced pathology in mice.
abstract: Chikungunya virus (CHIKV) infection is a re-emerging pandemic human arboviral disease. CD4+T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+T cells due to the induction of anergy in CHIKV-specific CD4+effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease.
  
  
  
  Chikungunya virus (CHIKV) has re-emerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, effective treatment is still inadequate. While T cells-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-IL-2 antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates the CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+ effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+ T cells through induction of anergy in CHIKV-specific CD4+ Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis and its expansion could control virus-mediated immunopathology.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Wendy W L
authors.initials: WW
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Teck-Hui
authors.initials: TH
authors.lastname: Teo
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Her
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Fok-Moon
authors.initials: FM
authors.lastname: Lum
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore.
authors.forename: Yiu-Wing
authors.initials: YW
authors.lastname: Kam
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore.
authors.forename: Doreen
authors.initials: D
authors.lastname: Haase
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Olaf
authors.initials: O
authors.lastname: Rötzschke
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Institute of Infection and Global Health, University of Liverpool, United Kingdom lisa_ng@immunol.a-star.edu.sg.
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng