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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.

SUBMITTER: Lee WW 

PROVIDER: S-EPMC5122839 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Virus infection drives IL-2 antibody complexes into pro-inflammatory agonists in mice.

Lee Wendy W L WW   Teo Teck-Hui TH   Lum Fok-Moon FM   Andiappan Anand K AK   Amrun Siti Naqiah SN   Rénia Laurent L   Rötzschke Olaf O   Ng Lisa F P LF  

Scientific reports 20161125


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<sup>+</sup  ...[more]

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