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?3). To examine if Tregs had been induced by OVA feeding, we removed CD25+ cells from selleck products the splenocytes; this resulted in significantly enhanced proliferation to OVA (Fig.?3, top panel). The conclusion that CD25+ Tregs were involved in the observed tolerization was supported by complete lack of effect on proliferation when splenocytes were obtained from the control-fed pIgR KO mice (Fig.?3, top panel). We next examined whether CD4+?CD25+ T cells from OVA-fed pIgR KO mice could transfer tolerance to na?ve WT mice. Tolerance in donor mice through the feeding protocol was confirmed by reduced DTH (data not shown). FACS-sorted CD4+?CD25+ and CD4+?CD25? splenic T cells from either OVA- or control-fed pIgR KO mice were transferred to na?ve WT mice (Fig.?4A). Delayed-type hypersensitivity to OVA and HSA was then measured in the recipients by ear skin challenge 3?weeks after s.c. sensitization with a mix of the two antigens. Wild-type mice that had received CD4+?CD25+ T cells from OVA-tolerized pIgR KO mice showed significant reduction of DTH to OVA (P?Endonuclease groups was revealed when we determined the levels of specific serum antibody or tested the in vitro proliferation against OVA and HSA (data not shown). The first study that examined a possible involvement Selleck EGFR inhibitor of intestinal IgA (coproantibodies) in mucosally induced systemic hyporesponsiveness was published in 1975 by the group of Heremans (20). Since then the involvement of IgA in allergy has been controversial although there is currently a focus on leaky epithelia in several immune-mediated diseases (21); a role of microbial stimulation and early antigen exposure for adequate tolerance induction is under intense debate (22). Here, we examined concurrently in pIgR KO mice how the absence of secretory antibodies influences immunological effector functions and oral tolerance. This mouse strain lacks both SIgA and SIgM and was shown to be predisposed to systemic anaphylaxis after parenteral sensitization, although suppressive mechanisms induced via the gut by first feeding the antigen (OVA) strikingly protected against this overreaction. In our model, tolerance was presumably induced in MLNs where tolerogenic conditioning of antigen-carrying dendritic cells (DCs) takes place (7). But Tregs become rapidly disseminated to peripheral lymph nodes by only partially understood homing mechanisms (23). There they can expand in parallel with helper/effector T cells when a continuous supply of cognate antigen is present (24) �C which was the case in our model with regard to OVA because of the s.c. FCA depots.