Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines
biorxiv(2020)
摘要
Environmental Enteric Dysfunction (EED) is an intestinal disease caused by malnutrition and infection that leads to malabsorption and stunting. EED is also associated with a reduced efficacy of oral vaccines. We show in a microbiota and diet-dependent model of EED that oral vaccine-specific CD4 T cell responses fail in the small intestine but responses in the draining lymph node were unaffected. Accordingly, the number of immunosuppressive RORγTFOXP3 T in the small intestine inversely correlated with the response to oral vaccination. Depletion of RORγTFOXP3 T indicated that they were necessary for EED-associated inhibition of the vaccine response. Additionally, RORγTFOXP3 T are important to regulate EED-associated inflammation as their depletion significantly worsened stunting. We have shown that EED-associated intestinal inflammation leads to a localized intestinal blockade of CD4 T cell immunity. These results support a modular model for immunity where tissue responses can be regulated independently of systemic immunity to prevent autoinflammation.
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关键词
vaccines,regulatory cells,enteropathy-induced
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