T cell repertoire alterations of vascularized xenografts

The role of T cells in the rejection of vascularized xenografts has been li ttle explored. Because of the high potential diversity of xenoantigens, it has been suggested that xenotransplantation could induce a strong cellular response that could contribute to delayed rejection. Alternatively, alterat ions in molecular interactions could impair the T cell response. Because th e analysis of TCR repertoire in vivo indirectly reflects the nature and the magnitude of T cell xenorecognition, we took advantage of the possibility of obtaining long term survival of hamster heart xenografts in rat recipien ts treated with a combination of cobra venom factor and cyclosporin A (CsA) , to analyze T cell infiltration and, for the first time, V beta TCR usage, at the complementarity-determining region 3 level, in accommodated and rej ected xenografts, compared with allografts, After withdrawal of CsA ton day 40), the analysis of V beta family expression and corresponding complement arity-determining region 3 lengths in rejected xenografts revealed a Gaussi an pattern, in contrast to a much more restricted pattern in rejected allog rafts (p = 0.002), suggesting that, after withdrawal of CsA, all the underr epresented T cell clones are rapidly expanded in xenografts, These results correlate with the rapid kinetics of rejection (4 +/- 1 days), the high num ber of T cells, the rapid expression of markers of activation (IL-2 recepto r alpha-chain and class II receptor), and the strong deposit of IgG Abs in rejected xenografts, Taken together, these results suggest that the intensi ty and diversity of the T cell response to xenografts could be stronger tha n the response to allografts in vivo.