title: Different patterns of TCR beta chain regulation following allo- and xeno-transplantation.
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 However, when CsA is withdrawn on day 40, an acute cellular rejection occurs within 4 +/- 1 days.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 Vbeta transcripts) and qualitative (CDR3 length distribution) assessment of the T cell receptor (TCR) beta 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 Vbeta transcripts was high in both rejected allo- and xenografts. However, whereas in xenografts acute rejection occurred without skewing of Vbeta 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 beta chain transcriptome, we show that some families can clusterize and can discriminate allo- or xeno-patterns at the level of both the number of Vbeta 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.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale (INSERM) - Unité 437: Immunointervention dans les Allo- et les Xénotransplantations, Institut de Transplantation Et de Recherche en Transplantation (I.T.E.R.T.), Nantes Cedex, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Guillet
authors.forename: Katia
authors.initials: K
authors.lastname: Gagne
authors.forename: David
authors.initials: D
authors.lastname: Lair
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Heslan
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Doré
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
mesh_terms: D000818:Animals; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D007700:Kinetics; D008297:Male; D005810:Multigene Family / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014183:Transplantation, Heterologous / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine