Combination regimens of FK778 with tacrolimus and mycophenolate mofetil in experimental cardiac transplantation

Abstract

were primary immunized with influenza vaccine 7-9 weeks prior to transplant in absence of immunosupression. A secondary boost immunization was administered during therapy with either IDEC-131 monotherapy (n 4), or CyA (controls, n 2). at day 14 post transplant. The antibody responses was measured against two influenza epitopes (H1N1, H3N2). Results: 5 out of 6 animals responded to the primary flu challenge by the production of IgM (5) and IgG (4). Despite intact primary responses, CyA completely abrogated the secondary Ab response in both animals. In contrast, all anti-CD154-treated animals (4/4) mounted a secondary IgM Ab response. The secondary IgG response was modulated by anti-CD154 blockade: absent in 2 animals, weak in 1, and robust in 1. Conclusion: As opposed to CyA, which completely inhibits the secondary response to influenza, CD154 blockade did not impair the ability of the graft recipient to mount a secondary response against influenza. If confirmed in a larger series and in the setting of chronic illness, this finding suggests that CD154 blockade spares important facets the recipients adaptive immunity against opportunistic infections, potentially conferring a clinically significant advantage over conventional immunosuppression with respect to common pathogens.