Tolerogenic T cells need probiotics: CD4 ⁺ CD8αα ⁺ double-positive intraepithelial lymphocytes (DP IELs) are a recently discovered class of intestinal T cells believed to take part in a variety of immune responses, including oral tolerance. These cells are absent in germ-free mice, but the mechanisms driving their development are unclear. Cervantes-Barragan et al. found that a particular species of probiotic bacteria, Lactobacillus reuteri , induces DP IELs. This does not occur by stimulating the immune system directly. Instead, L. reuteri generates a specific derivative of dietary tryptophan that promotes differentiation of DP IEL precursors. These findings underscore the delicate interplay between benign bacteria, diet, and gut health. Science , this issue p. 806

Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.

Helicobacter in the intestine induce regulatory T cells during homeostasis and effector T cells during colonic inflammation.

Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103⁺ gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter-specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103⁺ and CD103^– migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103⁺ migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103^– DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is ‘dominant’, necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.