How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.
Animals ; Basophils ; Immunization ; Interleukin-3 ; Interleukin-4* ; Lymph Nodes ; Mice ; Papain ; Parasites ; Receptors, Interleukin-3 ; T-Lymphocytes

Immunobiological roles of schistosome eggs during murine experimental infection were investigated with special reference to the induction of basophilic leukocytes. After single- or bisexual infection with Schistosoma mansoni in BALB⁄c mice, splenomegaly and liver granulomas were observed only in bisexual infection in parallel with deposition of mature parasite eggs. Comparison of the kinetics of basophil response revealed a marked increase in number in the bone marrow of mice with bisexual infection at the 7^th week post infection as opposed to a marginal increase in single- sex infections. In the spleen, bimodal response was observed in the basophil responses; a small but repeatable peak at the 4^th week after infection, increasing again at the 8^th week, which corresponded to the initiation and maturation of parasite eggs in the affected organs of infected mice. The same time course was observed for IL-4 production by the splenocytes from mice of bisexual infection. To obtain more concrete evidence of the role of eggs in the induction of basophils, we tested using the intravenous egg injection model. Injection of eggs induced basophilia, and it was accompanied by the up-regulation of IL-4 production in splenocytes from the 8^th day. Basophils induced in this model showed a high level of IL-4 production confirmed by flow cytometry, while faint levels of IL-4 production were observed for CD4⁺ T cells at this time point. In addition, we demonstrate that egg deposition is the trigger of basophil induction and activation in the murine experimental model of S. mansoni infection, which might play an essential role in the initiation of Th1⁄2 conversion during the course of S. mansoni infection in vivo.