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

2004; Wiley; Volume: 11; Issue: 4 Linguagem: Inglês

10.1111/j.1399-3089.2004.00136.x

1399-3089

Marina Guillet, Katia Gagne, David Lair, Jean‐Marie Heslan, Jean‐Christophe Doré, Jean‐Paul Soulillou, Sophie Brouard,

Renal Transplantation Outcomes and Treatments

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 However, when CsA is withdrawn on day 40, an acute cellular rejection occurs within 4 ± 1 days.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 V β 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 V β transcripts was high in both rejected allo‐ and xenografts. However, whereas in xenografts acute rejection occurred without skewing of V β 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 V β 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.