Litomosoides sigmodontis induces TGF‐β receptor responsive, IL‐10‐producing T cells that suppress bystander T‐cell proliferation in mice

Helminth parasites suppress immune responses to prolong their survival within the mammalian host. Thereby not only helminth‐specific but also nonhelminth‐specific bystander immune responses are suppressed. Here, we use the murine model of Litomosoides sigmodontis infection to elucidate the underlying mechanisms leading to this bystander T‐cell suppression. When OT‐II T cells specific for the third‐party antigen ovalbumin are transferred into helminth‐infected mice, these cells respond to antigen‐specific stimulation with reduced proliferation compared to activation within non‐infected mice. Thus, the presence of parasitic worms in the thoracic cavity translates to suppression of T cells with a different specificity at a different site. By eliminating regulatory receptors, cytokines, and cell populations from this system, we provide evidence for a two‐staged process. Parasite products first engage the TGF‐β receptor on host‐derived T cells that are central to suppression. In a second step, host‐derived T cells produce IL‐10 and subsequently suppress the adoptively transferred OT‐II T cells. Terminal suppression was IL‐10‐dependant but independent of intrinsic TGF‐β receptor‐ or PD‐1‐mediated signaling in the suppressed OT‐II T cells. Blockade of the same key suppression mediators, i.e. TGF‐β‐ and IL‐10 receptor, also ameliorated the suppression of IgG response to bystander antigen vaccination in L. sigmodontis‐infected mice.