LOVE this sort of stuff, but wouldn't post it (preclinical, not oncology) to this thread if not for the portion which I've empasized.... news to me!.....
Clin Exp Immunol. 2013 Feb 20. doi: 10.1111/cei.12091. [Epub ahead of print]
Indoleamine 2,3 dioxygenase contributes to transferable tolerance in rat RBC inducible model of experimental autoimmune haemolytic anaemia.
Dahal LN, Hall LS, Barker RN, Ward FJ.
Section of Immunology and Infection, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Autoimmune haemolytic anaemia (AIHA) is caused by autoantibodies against RBC surface antigens that render RBC susceptible to Fc-mediated phagocytosis and complement-mediated lysis. Experimental AIHA can be induced by injection of rat RBC to naïve mice but a lymphocyte-mediated regulatory mechanism eventually suppresses the production of autoantibodies specific for mouse RBC. Critically, this tolerogenic response can be transferred to naïve mice by splenocytes from the rat RBC immunized mouse. Here we investigate whether Indoleamine 2,3 dioxygenase (IDO) or the initiators of IDO cascade, including the CTLA-4 receptor and its soluble isoform contribute to this tolerogenic mechanism. Splenocytes from experimental AIHA mice were adoptively transferred to naive mice under the cover of anti-CTLA-4, anti-soluble CTLA-4 antibodies or IDO inhibitor 1-Methyl Tryptophan (1-MT). Recipient mice were immunized with rat RBC and levels of antibody against self-RBC and rat-RBC were monitored. Our results indicate that transfer of tolerance to naïve recipients is dependent on IDO mediated immunosuppression as mice receiving previously tolerized splenocytes under the cover of 1-MT were refractory to tolerance and developed haemolytic disease upon further challenge with rat RBC. Initiators of IDO activity, CTLA-4 or soluble CTLA-4 did not mediate this tolerogenic process but on their blockade, boosted antigen-specific effector immune responses |
