Sodium cromoglycate treatment of CD200R1KO.CD200tg mice enhances graft survival (P2154)

Abstract

Abstract Allograft survival is not increased in CD200R1KO mice, lacking the primary inhibitor receptor for CD200, unlike in CD200tg mice. Rejection in both control, and CD200R1KO mice is associated with graft infiltration by activated mast cells, with evidence for degranulation (>80%). There is evidence that alternate CD200Rs in mice can contribute to immunosuppression through altered dendritic cell differentiation, and enhanced induction of Foxp3+Tregs. We asked whether, in CD200R1KO.CD200tg mice, attenuation of mast cell degranulation by sodium cromoglycate could foster enhanced graft survival following induction of Tregs. BALB/c skin grafts were transplanted to 10/group control, CD200tg or CD200R1KO.CD200tg mice, with/without treatment with cromoglycate (150mg/Kg, alternate days). All animals received low-dose rapamycin (0.5mg/Kg), previously shown to prolong survival only in CD200tg mice. Graft survival was monitored daily from d10, and splenic MLC responses measured in vitro on d14/21. Immunohistology was performed on all grafted tissue at d14. Graft survival was increased only in CD200tg mice, and in CD200R1KO.CD200tg mice receiving cromoglycate (p<0.05). This was accompanied by decreased degranulation of graft-infiltrating mast cells, and increased Foxp3+Treg infiltration. Survival was abolished by ongoing infusion of neutralizing anti-CD200 mAb, or infusion of anti-CD200R1/2mAb (in CD200tg or CD200R1KO.CD200tg mice respectively).