Different patterns of TCR β chain regulation following allo‐ and xeno‐transplantation

Publisher Website
Google Scholar
Abstract
Background: In the concordant hamster‐to‐rat cardiac xenograft model, recipients treated with cobra venom factor for the first 10 days following transplantation and daily with Cyclosporine A (CsA) do not reject their grafts. However, when CsA is withdrawn on day 40, an acute cellular rejection occurs within 4 ± 1 days. Allografts performed in the same conditions are rejected within 18 ± 4 days. Methods: In this model, we have compared graft infiltrating T cells through both a quantitative (number of Vβ transcripts) and qualitative (CDR3 length distribution) assessment of the T cell receptor (TCR) β chain transcriptome in allo‐ and xeno‐transplantations. Results: We report striking differences in TCR usage at day 15 following allo‐ and xeno‐transplantation as well as during rejection following CsA withdrawal. The number of Vβ transcripts was high in both rejected allo‐ and xenografts. However, whereas in xenografts acute rejection occurred without skewing of Vβ CDR3 length distribution, T cells infiltrating allografts during rejection after CsA interruption had a highly altered CDR3 length distribution pattern. In addition, using a correspondence factor analysis of the β chain transcriptome, we show that some families can clusterize and can discriminate allo‐ or xeno‐patterns at the level of both the number of Vβ transcripts and the CDR3 length distribution. Conclusions: Our data show that, in vivo, even in the hamster‐to‐rat concordant combination, the anti‐xenograft T cell response is strong and will likely represent another challenge for xenotransplantation.