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

Abstract

ObjectiveTo 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.MethodsNippostrongylus 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.ResultsParasite-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.InterpretationThe 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.

Regulatory T cell monitoring in severe eosinophilic asthma patients treated with mepolizumab

“…In animal models of autoimmunity and parasitic infection, the promotion of the Treg by IL-5 has been reported and this effect was abrogated using an anti-IL-5 antibodies, suggesting a positive regulatory effect of IL-5 on Treg production. 20,21 However, human and mice may be different and this pioneer study supports a possible negative regulatory effect of IL-5 on Treg after mepolizumab treatment in SEA patients. The role of CD8+ cells was also investigated in relation to the pathogenesis of asthma.…”

“…It is now available and indicated for SEA patients over 12 years of age 16‐19 and has been demonstrated to improve control of asthma in patients with a peripheral eosinophil count >300 cell/mm 3 19 . The mechanisms of interaction of IL‐5 and Treg cells are still controversial 20,21 …”

“…19 The mechanisms of interaction of IL-5 and Treg cells are still controversial. 20,21 However, no data showing the effect of mepolizumab on Tregs and other T cell subsets, including, CD8, CD19 and NK, is yet available in the literature.…”

Mesenchymal PGD2 activates an ILC2-Treg axis to promote proliferation of normal and malignant HSPCs

“…Since IL-5 promotes generation of antigen-specific CD4 + CD25 + T regulatory cells (Tregs, 35 , 36 ), and since emerging evidence suggests that Tregs function as an important component of the supporting niche for HSPCs ( 37 , 38 ), we wondered if the ILC2s/IL-5-Treg signaling axis was the underlying mechanism of mesenchymal PGD 2 -mediated HSC proliferation. We first compared the frequencies of CD4 + CD25 + Tregs in the co-culture of normal CD34 + HSPCs on HD and AML MSCs.…”

A critical analysis of helminth immunotherapy in multiple sclerosis

“…This includes dosage and timing of inoculation with larvae, ova, or excreted-secreted (E/S) products from 12 different helminthic species, and adoptive transfer of leukocytes treated with E/S products or isolated from helminth-infected animals into mice or rats prior to or after EAE immunization (Figure 1, Table 1). 13–35…”