ICOS-Ig combined with subclinical dose of CsA induces long term survival of mouse cardiac allografts / 中华器官移植杂志

ABSTRACT

Objective To investigate the potential role of IC0s-Ig and CsA in inducing transplantation tolerance and the mechanisms thereof. Methods ICOS-Ig was a fusion protein of human ICOS extracellular region and IgG Fc fragment.Cardiac allograft from BALB/c mouse was transplanted to C57BL/6 mouse Animals were randomly divided into 5 groups(1) un-treated group;(2)IgG-treated group,250g,i.p.day 2,4,6;(3)ICOS Ig-treated group,250g,i.P.day 2,4,6;(4) CsA-treated group,10 mg/kg,i.p.day 0-6;(5)ICOS-Ig+CsA-treated group.The survival time and pathological changes of the cardiac allografts were monitored.The mixed lymphoeyte reaction (MLR) and the alloantibody level of the recipients were also detected.Results The median survival time (MST) of the cardiac allografts was (8.5±1.5) days in un-treated group,(8.0±0.8) days in IgG-treated group,(29.5±7.7) days in ICOS-Ig-treated group,and(21.0±5.0) days in CsA-treated group.respectively.In ICOS-Ig + CsA-treated group,the MST was prolonged to longer than 100 days,which was significantly longer than other four groups(P<0.01).Allogeneic hearts from ICOS-Ig and/or CsA immunized recipients revealeel milder histological changes than control groups(P<0.05).Mechanical ahalysis revealed that splenic T cells from recipients also exhibited depressed MLR activities.The alloantibody level in ICOS-Ig-treated group and/or CsA-treated group was lower than in control groups(P<0.05),suggesting ICOS-Ig not only inhibited cell immunity,but also depressed humoral response.Conclusion ICOS-Ig combined with CsA leads to a long-term survival of mouse cardiac allografts.The induced tolerance is donor-specific and the mechanisms may be associated with T cell anergy.