Recombinant IFN-γ abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production
✍ Scribed by Régis Josien; Maria-Cristina Cuturi; Patrice Douillard; Michèle Heslan; Jean-Marie Heslan; Jean-Paul Soulillou
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 183 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Donor-specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donorspecific blood transfusion (DST). We previously showed that this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount an efficient anti-donor humoral response whereas transfer of sera from rejecting animals triggered rejection in tolerant animals. This tolerance can be abrogated by daily post-graft administration of recombinant IFN-+ (rIFN-+ ). To elucidate the mechanisms of action of rIFN-+ , T cell, macrophage and B cell functions were assessed in allograft recipients. IFN-+ did not restore the expression of Th1-related cytokine mRNA or the activated macrophage product inducible nitric oxide synthase in allografts. Importantly, rIFN-+ treatment promptly restored the anti-donor humoral response in DST-treated recipients. We conclude that rIFN-+ treatment in DST-treated allograft recipients cannot reverse the unresponsive state of Th1 cells and macrophages infiltrating the graft, but can provide B cell help for IgG alloantibody production which is lacking in these animals.