10 Rag2−/−) are adoptively transferred into lymphopenic hosts that express their cognate antigen, chicken ovalbumin, as a soluble protein in the bloodstream (sOva Rag2−/−). The combination of antigen and lymphopenia results in massive donor T-cell expansion, leading to multiorgan infiltration and lethal autoimmune disease mediated by Th1- and Th17-type effector T cells [14]. To determine whether Th2-type cytokines also play a role in this pathology, we BIBW2992 performed adoptive transfers and measured IL-4 and IL-13 by intracellular flow cytometry. These studies showed that, while unable to produce IL-4, a large fraction

of the donor T cells could produce IL-13 both during the onset (day 3) and peak (day 7) of disease. Many donor T cells were positive for IFN-γ and IL-17, which is consistent with previous work [14, 15], and few were positive for IL-2 (Fig. 1A). Having established that donor T cells produce IL-13 in sOva Rag2−/− Ensartinib purchase hosts, we next asked whether they coexpress other cytokines. Surprisingly, we found that IL-13 often segregated with IFN-γ and IL-17 (Fig. 1B), the signature cytokines of Th1- and Th17-type effectors

[2, 6]. To ask whether IL-13-producing Th1 and Th17 cells can be generated in the absence of lymphopenia or systemic inflammation, we transferred DO11.10 Rag2−/− T cells into congenic, lymphoreplete mice, then immunized with Ova-pulsed antigen presenting cells (APCs). In contrast to sOva Rag2−/− hosts, we could detect donor T cells expressing both IL-4 and IL-13 in these immunized hosts, which demonstrates that our immunization protocol does induce “classical” Selleckchem Fludarabine Th2-type effectors. We could also detect IL-13+ donor T cells coexpressing either IFN-γ or IL-17, which confirms that IL-13-producing Th1 and Th17 cells can be generated in the context of

“protective” immune responses. In fact, on a per cell basis, the percentage of Th1 and Th17 cells producing IL-13 was comparable between immunized and autoimmune sOva Rag2−/− hosts (Fig. 1C and D). It should also be noted that, overall, the percentage of IL-13+ cells was far greater than that of IL-4+, IFN-g+, or IL-17+ cells, which suggests that IL-13 can be produced either alone or in concert with unidentified cytokines. Coexpression of IFN-γ and IL-17 was seen in sOva Rag2−/− hosts but not immunized hosts, which suggests a link to autoimmunity, and coexpression of IL-17A and IL-17F was common to both models (Supporting Information Fig. 2). To ask whether IL-13-producing Th1 and Th17 cells can be generated during polyclonal T-cell responses, we used a model of chemically induced colitis where T cells are primed in response to a range of microbial and self-antigens. First, we determined that, compared to untreated controls, DSS-treated mice had increased numbers of IL-13+ CD4+ TCRβ+ cells within mesenteric lymph nodes (Supporting Information Fig. 3).