Different patterns of TCR beta chain regulation following allo- and xeno-transplantation.
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 However, when CsA is withdrawn on day 40, an acute cellular rejection occurs within 4 +/- 1 days.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.
Guillet
Marina
M
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.
Gagne
Katia
K
Lair
David
D
Heslan
Jean-Marie
JM
Doré
Jean-Christophe
JC
Soulillou
Jean-Paul
JP
Brouard
Sophie
S
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
D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine