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Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation.

ABSTRACT: Numerous population studies and experimental models suggest that helminth infections can ameliorate immuno-inflammatory disorders such as asthma and autoimmunity. Immunosuppressive cell populations associated with helminth infections include Treg and alternatively-activated macrophages. In previous studies, we showed that both CD4(+)CD25(+) Treg, and CD4(-) MLN cells from Heligmosomoides polygyus-infected C57BL/6 mice were able to transfer protection against allergic airway inflammation to sensitized but uninfected animals. We now show that CD4(-)CD19(+) MLN B cells from infected, but not naïve, mice are able to transfer a down-modulatory effect on allergy, significantly suppressing airway eosinophilia, IL-5 secretion and pathology following allergen challenge. We further demonstrate that the same cell population can alleviate autoimmune-mediated inflammatory events in the CNS, when transferred to uninfected mice undergoing myelin oligodendrocyte glycoprotein((p35-55))-induced EAE. In both allergic and autoimmune models, reduction of disease was achieved with B cells from helminth-infected IL-10(-/-) donors, indicating that donor cell-derived IL-10 is not required. Phenotypically, MLN B cells from helminth-infected mice expressed uniformly high levels of CD23, with follicular (B2) cell surface markers. These data expand previous observations and highlight the broad regulatory environment that develops during helminth infections that can abate diverse inflammatory disorders in vivo.

SUBMITTER: Wilson MS

PROVIDER: S-EPMC3179601 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation.

Wilson Mark S MS Taylor Matthew D MD O'Gorman Mary T MT Balic Adam A Barr Tom A TA Filbey Kara K Anderton Stephen M SM Maizels Rick M RM

European journal of immunology 20100601 6

Numerous population studies and experimental models suggest that helminth infections can ameliorate immuno-inflammatory disorders such as asthma and autoimmunity. Immunosuppressive cell populations associated with helminth infections include Treg and alternatively-activated macrophages. In previous studies, we showed that both CD4(+)CD25(+) Treg, and CD4(-) MLN cells from Heligmosomoides polygyus-infected C57BL/6 mice were able to transfer protection against allergic airway inflammation to sensi ...[more]

PMID: 20306466

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Project description:BackgroundThe recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.Methodology/principal findingsWe compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.Conclusion/significanceT. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.

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Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation.

Publications

Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation.

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