Abstract:
BACKGROUND:CD154 mediates key facets of humoral and cellular immunity to alloantigens, and is tolerogenic to influenza antigens in primates. Barriers to CD154-based tolerance induction for primate cardiac allografts have not previously been defined. METHODS:Heterotopic cardiac allograft outcomes in cynomolgus monkeys treated with a CD154 inhibitor, IDEC-131 (n=27), were compared to no treatment (n=4) or cyclosporine A (n=6). RESULTS:CD154 blockade significantly prolonged median allograft survival, from 6.2 (range 6, 7, n=4) days in untreated controls, to 39 (8,112, n=16) days with intensive monotherapy and 93 (>25, 386; n=3) days with added antithymocyte globulin (ATG), but did not yield tolerance. Alloantibody production was delayed but not prevented by IDEC-131 alone or with ATG, and was exacerbated by infusion of donor bone marrow (n=8). Expression of ICOS was prominent in graft infiltrating lymphocytes, and preceded elaboration of antidonor antibody and vasculopathy. CONCLUSION:CD154 monotherapy modulates primate cardiac alloimmunity, but does not readily induce tolerance. Targeting alternative costimulation pathways, including ICOS, may facilitate tolerance induction based on CD154 blockade.
journal_name
Transplantationjournal_title
Transplantationauthors
Azimzadeh AM,Pfeiffer S,Wu G,Schröder C,Zorn GL 3rd,Kelishadi SS,Ozkaynak E,Kehry M,Atkinson JB,Miller GG,Pierson RN 3rddoi
10.1097/01.tp.0000190099.62847.e6subject
Has Abstractpub_date
2006-01-27 00:00:00pages
255-64issue
2eissn
0041-1337issn
1534-6080pii
00007890-200601270-00017journal_volume
81pub_type
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