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These data provide evidence that PH in leptospirosis may not be related only to autoimmune mechanisms.Ī potential role for autoimmunity in leptospirosis-associated PH was suggested based on observations in the guinea pig model of leptospirosis ( 12) and, to a lesser extent, in human patients with severe pulmonary hemorrhage syndrome ( 7). Of note, the absence of functional B- and T-cell lymphocytes did not preclude the occurrence of PH. In conclusion, the loss of the Inos gene had a negligible effect on the outcome of leptospiral infection, although we observed a reduced susceptibility for interstitial nephritis in this group. There was no evidence of PH in the WT controls. PH was observed in 57 and 94% of Rag1 KO mice and in 83 and 100% of SCID mice, using inoculum doses of 10 7 and 10 6 leptospires, respectively. All of the Rag1 KO and SCID animals died of acute leptospirosis, whereas all of the WT mice survived. The frequency and severity of nephritis was significantly lower in the Inos KO mice. The Inos KO and WT mice survived with no clinical symptoms of leptospirosis. The animals used were Inos KO mice, recombination activating gene 1 ( Rag1) KO mice, CB17 severe combined immunodeficiency (SCID) mice, and the respective wild-type (WT) C57BL/6 and BALB/c controls. We studied the outcome of infection by the virulent Leptospira interrogans serovar Copenhageni strain Cop. This record has no associated files available for download.The aims of this study were to investigate the frequency of pulmonary hemorrhage (PH) in mice unable to produce functional B and T lymphocytes and to explore the effect of an inducible nitric oxide synthase gene ( Inos) knockout (KO) on the frequency/severity of interstitial nephritis in vivo. We conclude from this that immunotherapeutics like HB2-SAPORIN would be more accurately assessed for intrinsic potency in NOD/SCID mice where the effects of NK cell and possibly other non-adaptive immune mechanisms would not have a significant influence. We reason that the complete lack of therapeutic effect of HB2 antibody and the reduced effect of HB2-SAPORIN in NOD/SCID mice is due to the reduced cytolytic activity of NOD/SCID NK cells which is probably below a certain critical threshold value in these animals. It was initially thought that the lack of therapeutic effect of antibody and IT in NOD-SCID-HSB-2 mice might relate to their putative lack of NK cells but flow cytometric and functional studies with NOD-SCID mouse splenocytes revealed that these animals do have some functional NK cells though fewer in number and possibly lower in functionality than those of SCID mice. In contrast HB2 antibody treatment of NOD/SCID-HSB-2 mice had no therapeutic effect in these animals and the therapeutic effectiveness of both HB2-SAPORIN and HB2-F(ab)2-SAPORIN ITs was similar and significantly reduced compared to the effect observed in SCID-HSB-2 mice. HB2 antibody treatment of SCID-HSB-2 mice also led to a significant prolongation in time to leukaemia development compared with sham-treated controls with 37% of animals in this treatment group disease-free at termination of the study. In contrast treatment with HB2-F(ab)2-SAPORIN was significantly less effective in SCID-HSB-2 mice with 80% of animals in this treatment group developing leukaemia over the course of the study. Treatment of SCID-HSB-2 mice with HB2-SAPORIN led to a significant prolongation in the time to development of signs and symptoms of disease compared with PBS sham-treated controls with 80% of animals surviving disease-free. 10 mug doses of the anti-CD7 antibody HB2 on days 7, 9 and 11 or with a single 10 mug dose of HB2-SAPORIN or a 7.4 mug dose of HB2-F(ab)2-SAPORIN immunotoxin (IT) on day 7. with two million human HSB-2 T-ALL cells on day 1 (SCID-HSB-2 and NOD/SCID-HSB-2 mice) and treated later with 3 i.v. Groups of 8 to ten SCID (CB.17 scid/scid) or NOD/SCID (NOD/LtSz- scid/scid) mice were injected i.v.
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