Accumulation of T cells with potent regulatory properties and restricted Vbeta7-TCR rearrangements in tolerated allografts.
BACKGROUND
We have previously demonstrated that a short-course treatment with LF15-0195, a 15-deoxyspergualin analogue, induces donor-specific tolerance of cardiac allografts in rats and expansion of splenic CD4CD25 regulatory T cells.


METHODS
To further characterize long-term tolerance in this model, we have analyzed the phenotype, regulatory properties and TCR-Vbeta usage of the T cells infiltrating the tolerated allografts.


RESULTS
We demonstrate that the tolerated allografts express high levels of FoxP3 transcripts and contain a large number of CD4 T cells, half of which express CD25. Moreover, T cells from these tolerated allografts are very powerful at transferring tolerance to a subsequent allograft recipient, demonstrating the presence of potent regulatory T cells at the site of the graft. Interestingly, the T cells infiltrating the tolerated allografts systematically display restricted Vbeta7 TCR rearrangements.


CONCLUSIONS
These results demonstrate in this model of tolerance, a specific accumulation of T cells with potent regulatory properties and exhibiting restricted Vbeta7-TCR rearrangements at the graft site.
Heslan
Jean-Marie
JM
Institut National de la Santé et de la Recherche Médicale Unité 643 (INSERM U643) and Institut de Transplantation Et de Recherche en Transplantation, CHU Hotel Dieu, Nantes, France.
Beriou
Gaëlle
G
Le Luduec
Jean-Benoît
JB
Guillonneau
Carole
C
Anegon
Ignacio
I
Soulillou
Jean-Paul
JP
Cuturi
Maria-Cristina
MC
Chiffoleau
Elise
E
D000818:Animals; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D006146:Guanidines / Q000494:pharmacology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology*
D006146:Guanidines; C434185:LF 150195; D016693:Receptors, Antigen, T-Cell, alpha-beta