Accumulation of T Cells with Potent Regulatory Properties and Restricted Vβ7-TCR Rearrangements in Tolerated Allografts

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Abstract
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. 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. 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. 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.