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Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells

Abstract

Allergic asthma is a chronic inflammatory disease and despite the introduction of potent and effective drugs, the prevalence has increased substantially over the past few decades1. The explanation that has attracted the most attention is the 'hygiene hypothesis', which suggests that the increase in allergic diseases is caused by a cleaner environment and fewer childhood infections2,3,4. Indeed, certain mycobacterial strains can cause a shift from T-helper cell 2 (Th2) to Th1 immune responses, which may subsequently prevent the development of allergy in mice5,6,7. Although the reconstitution of the balance between Th1 and Th2 is an attractive theory, it is unlikely to explain the whole story, as autoimmune diseases characterized by Th1 responses can also benefit from treatment with mycobacteria and their prevalence has also increased in parallel to allergies8. Here we show that treatment of mice with SRP299, a killed Mycobacterium vaccae-suspension, gives rise to allergen-specific CD4+CD45RBLo regulatory T cells, which confer protection against airway inflammation. This specific inhibition was mediated through interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), as antibodies against IL-10 and TGF-β completely reversed the inhibitory effect of CD4+CD45RBLo T cells. Thus, regulatory T cells generated by mycobacteria treatment may have an essential role in restoring the balance of the immune system to prevent and treat allergic diseases.

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Figure 1: Effect of SRP299 treatment on the OVA-induced eosinophilic inflammation and cytokine production by splenocytes.
Figure 2: Transfer of SRP299-treated cells inhibit the OVA-induced eosinophilic inflammation and bronchial hyperresponsiveness in an allergen-specific manner.
Figure 3: The inhibitory effect of regulatory T cells resides within the CD4+CD45RBLo population and is mediated by IL-10 and TGF-β.

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Acknowledgements

We thank J. Lee, A. Nicholls and G. Dubois for technical support.

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Correspondence to Claudia Zuany-Amorim.

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L.R.B., G.B. and G.R. are employed by SR Pharma, the company that produces the heat-killed Mycobacterium vaccae.

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Zuany-Amorim, C., Sawicka, E., Manlius, C. et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 8, 625–629 (2002). https://doi.org/10.1038/nm0602-625

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