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2017 ; 8
(ä): 1453
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Interleukin-5 Mediates Parasite-Induced Protection against Experimental
Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific
CD4(+)CD25(+) T Regulatory Cells
#MMPMID29163523
Tran GT
; Wilcox PL
; Dent LA
; Robinson CM
; Carter N
; Verma ND
; Hall BM
; Hodgkinson SJ
Front Immunol
2017[]; 8
(ä): 1453
PMID29163523
show ga
OBJECTIVE: 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. METHODS: Nippostrongylus brasiliensis
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(+) T cells. Reactivity of CD4(+)CD25(+) T
regulatory cells from these animals was examined. RESULTS: 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(+)CD25(+) T regulatory cells earlier than EAE controls and
these expressed more Il5ra than controls. Treatment with IL-5 also reduced the
severity of EAE and induced Il5ra expressing CD4(+)CD25(+) T regulatory cells.
INTERPRETATION: 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(+)Il5ra(+) 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.