AUTHOR=Tran Giang T. , Wilcox Paul L. , Dent Lindsay A. , Robinson Catherine M. , Carter Nicole , Verma Nirupama D. , Hall Bruce M. , Hodgkinson Suzanne J. 

TITLE=Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4+CD25+ T Regulatory Cells

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01453

DOI=10.3389/fimmu.2017.01453

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Objective</title><p>To examine if the protective effect of parasite infection on experimental autoimmune encephalomyelitis (EAE) was due to interleukin (IL)-5, a cytokine produced by a type-2 response that induces eosinophilia. We hypothesize that, in parasite infections, IL-5 also promotes expansion of antigen-specific T regulatory cells that control autoimmunity.</p></sec><sec id="ST2"><title>Methods</title><p><italic>Nippostrongylus brasiliensis</italic> larvae were used to infect Lewis rats prior to induction of EAE by myelin basic protein. Animals were sham treated, or given blocking monoclonal antibodies to interleukin 4 or 5 or to deplete CD25<sup>+</sup> T cells. Reactivity of CD4<sup>+</sup>CD25<sup>+</sup> T regulatory cells from these animals was examined.</p></sec><sec id="ST3"><title>Results</title><p>Parasite-infected hosts had reduced severity and length of EAE. The beneficial effect of parasitic infection was abolished with an anti-IL-5 or an anti-CD25 monoclonal antibody (mAb), but not anti-IL-4 mAb. Parasite-infected animals with EAE developed antigen-specific CD4<sup>+</sup>CD25<sup>+</sup> T regulatory cells earlier than EAE controls and these expressed more <italic>Il5ra</italic> than controls. Treatment with IL-5 also reduced the severity of EAE and induced <italic>Il5ra</italic> expressing CD4<sup>+</sup>CD25<sup>+</sup> T regulatory cells.</p></sec><sec id="ST4"><title>Interpretation</title><p>The results of this study suggested that IL-5 produced by the type-2 inflammatory response to parasite infection promoted induction of autoantigen-specific CD25<sup>+</sup><italic>Il5ra</italic><sup>+</sup> T regulatory cells that reduced the severity of autoimmunity. Such a mechanism may explain the protective effect of parasite infection in patients with multiple sclerosis where eosinophilia is induced by IL-5, produced by the immune response to parasites.</p></sec>