Basophils are associated with T helper 2 (Th2) cell-polarized immune responses such as allergic disorders or helminth infections. To directly address the role of basophils for type 2 immunity, we generated transgenic mice with constitutive and selective deletion of basophils. Differentiation and accumulation of Th2 cells, induction of eosinophilia, and increase in serum IgE or IgG1 induced by allergens or by infection with the helminth Nippostrongylus brasiliensis appeared to be basophil independent. Further, basophils were not required for passive IgE- or IgG1-mediated systemic anaphylaxis. However, basophils were essential for IgE-meditated chronic allergic dermatitis and for protection against secondary infection with N. brasiliensis. These results demonstrate that basophils play an important role for protective immunity against helminths and orchestrate chronic allergic inflammation, whereas primary Th2 cell responses can operate efficiently in the absence of this cell type.

Stimulation of the immune system by pathogens, allergens, or autoantigens leads to differentiation of CD4+ T cells with pro- or anti-inflammatory effector cell functions. Based on functional properties and expression of characteristic cytokines and transcription factors, effector CD4+ T cells have been grouped mainly into Th1, Th2, Th17, and regulatory T (Treg) cells. At least some of these T cell subsets remain responsive to external cues and acquire properties of other subsets, raising the hope that this functional plasticity might be exploited for therapeutic purposes. In this study, we used an Ag-specific adoptive transfer model and determined whether in vitro-polarized or ex vivo-isolated Th1, Th17, or Treg cells can be converted into IL-4–expressing Th2 cells in vivo by infection of mice with the gastrointestinal helminth Nippostrongylus brasiliensis. Th1 and Th17 cells could be repolarized to acquire the expression of IL-4 and lose the expression of their characteristic cytokines IFN-γ and IL-17A, respectively. In contrast, both in vitro-generated and ex vivo-isolated Treg cells were largely resistant to repolarization. The helminth-induced conversion of Th1 or Th17 cells into Th2 cells may partially explain the inverse correlation between helminth infection and protection against autoimmune disorders.

Human cytomegalovirus (HCMV) is a human pathogen that causes severe disease primarily in the immunocompromised or immunologically immature individual. To date, no vaccine is available. We describe use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination. To generate a spread-deficient MCMV, the conserved, essential gene M94 was deleted. Immunization with MCMV-⌬M94 is apathogenic and protective against wild-type challenge even in highly susceptible IFN␣␤R ؊/؊ mice. MCMV-⌬M94 was able to induce a robust CD4؉ and CD8 ؉ T-cell response as well as a neutralizing antibody response comparable to that induced by wild-type infection. Endothelial cells were identified as activators of CD8 ؉ T cells in vivo. Thus, the vaccination with a spread-deficient betaherpesvirus is a safe and protective strategy and allows the linkage between cell tropism and immunogenicity. Furthermore, genomes of MCMV-⌬M94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance.

SummaryThe parasitic gastrointestinal nematode Nippostrongylus brasiliensis induces massive expansion of T helper type 2 (Th2) cells in the lung and small intestine. Th2 cells are a major source of interleukin-4 and interleukin-13, two cytokines that appear essential for rapid worm expulsion. It is unclear whether all Th2 cells induced during infection are pathogenspecific because Th2 cells might also be induced by parasite-derived superantigens or cytokine-mediated bystander activation. Bystander Th2 polarization could explain the largely unspecific B-cell response during primary infection. Furthermore, it is not known whether protective immunity depends on a polyclonal repertoire of T-cell receptor (TCR) specificities. To address these unresolved issues, we performed adoptive transfer experiments and analysed the TCR-Vb repertoire before and after infection of mice with the helminth N. brasiliensis. The results demonstrate that all Th2 cells were generated by antigen-specific rather than superantigen-driven or cytokine-driven activation. Furthermore, we show that worm expulsion was impaired in mice with a limited repertoire of TCR specificities, indicating that a polyclonal T-cell response is required for protective immunity.