The Greatest Drawback To the Myth Around Endonuclease Uncovered
002). The response to HSA in the OVA-fed and jointly sensitized pIgR KO mice only tended to be reduced for some isotypes, especially Endonuclease IgG1, IgG2a, and IgA (Fig.?1B). This was not the case in the three surviving tolerized mice given separate sensitization (Table?1); while their anti-OVA titers were similar to the jointly sensitized and tolerized pIgR KO mice (ELISA units: 13?000, 15?000, and 19?000), their anti-HSA titers were in the upper range of control-fed pIgR mice (ELISA units: 190?000, 210?000, and 230?000). To determine whether mucosally induced tolerance was mediated by active suppression (i.e., Tregs) in pIgR KO mice, we measured the cellular response to OVA and HSA. We also performed T-cell depletion in vitro and assessed tolerance in na?ve WT mice after adoptive cell transfer from OVA- or control-fed pIgR KO mice as a functional read-out for Tregs (see later). find more Groups of pIgR KO and WT mice fed OVA-containing diet or ordinary control pellets for 1?week, were s.c. sensitized by mixed OVA and HSA and then intradermally challenged with the two antigens in different ears to measure the T-cell helper/effector function by DTH reaction revealed as ear swelling (Table?1). After oral tolerization, both pIgR KO and WT mice showed significantly weaker DTH both to OVA and HSA than control-fed mice, particularly when the reaction was normalized in relation to the pre-challenge ear thickness (Fig.?2). Importantly, the tolerized pIgR KO mice showed much more pronounced suppression of OVA hypersensitivity (P?ABT-263 nmr mice �C with an individual difference generally more than 10%�C despite a trend towards stronger DTH reaction in control-fed pIgR KO mice than in WT controls (Fig.?2). Conversely, bystander suppression of HSA hypersensitivity after joint antigen sensitization was similar in OVA-tolerized pIgR KO and the WT counterparts (Fig.?2). However, in the three surviving pIgR KO mice sensitized separately with OVA and HSA in different hind legs (Table?1), the DTH was strikingly different after OVA feeding; while suppression to this antigen was the same as in jointly sensitized (OVA?+?HSA) animals, the DTH to HSA remained exactly at the level seen in control-fed pIgR KO mice �C consistent with the high levels of IgG1 antibodies against HSA and susceptibility to anaphylaxis after separate sensitization with the two antigens (Table?1). Thus, bystander suppression in all three read-outs appeared to depend on concurrent T-cell encounter with both antigens in lymph nodes draining the sensitizing injection site, making these results of interest despite the small test group. To address the mechanism for downregulated T-cell helper/effector activity revealed by reduced DTH (Fig.?2), we performed proliferation assays with splenocytes from OVA-fed pIgR KO mice sensitized to OVA and HSA.
