Accumulation of T cells with potent regulatory properties and restricted Vβ7-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 CD4(+)CD25(+) regulatory T cells. Methods. To further characterize long-term tolerance in this model, we have analyzed the phenotype, regulatory properties and TCR-V beta 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 V beta 7 TCR rearrangements. Conclusion. These results demonstrate in this model of tolerance, a specific accumulation of T cells with potent regulatory properties and exhibiting restricted V beta 7-TCR rearrangements at the graft site.