title: Virus infection drives IL-2 antibody complexes into pro-inflammatory agonists in mice.
abstract: The use of IL-2/JES6-1 Ab complex (IL-2 Ab Cx) has been considered as a potential therapeutic for inflammatory diseases due to its selective expansion of regulatory T cells (Tregs) in mice. Here, IL-2 Ab Cx was explored as a therapeutic agent to reduce joint inflammation induced by chikungunya virus, an alphavirus causing debilitating joint disease globally. Virus-infected mice treated with IL-2 Ab Cx exhibited exacerbated joint inflammation due to infiltration of highly activated CD4+effector T cells (Teffs). Virus infection led to upregulation of CD25 on the Teffs, rendering them sensitive towards IL2 Ab Cx. Ready responsiveness of Teffs to IL-2 was further demonstrated in healthy human donors, suggesting that the use of IL-2 Ab Cx in humans is not suitable. Changes in IL-2 sensitivity during active virus infection could change the responsive pattern towards the IL-2 Ab Cx, resulting in the expansion of pro-inflammatory rather than anti-inflammatory responses.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore 138648, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, 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 138648, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, 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 138648, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, 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 138648, Singapore.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Andiappan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore 138648, Singapore.
authors.forename: Siti Naqiah
authors.initials: SN
authors.lastname: Amrun
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore (A*STAR), Singapore 138648, Singapore.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, 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 138648, Singapore.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, 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 138648, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D065632:Chikungunya Fever / Q000276:immunology* / Q000821:virology*; D002646:Chikungunya virus / Q000502:physiology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007596:Joints / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D007376:Interleukin-2