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Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité 437: "Immunointervention dans les Allo et Xénotransplantations" and Institut de Transplantation et de Recherche en Transplantation (ITERT), Centre Hospitalier Universitaire-Hotel Dieu, Nantes, France;
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel;
Brigham and Women’s Hospital, Boston, MA 02115; and
§
Service d’Anatomopathologie, Centre Hospitalier Universitaire-Hotel Dieu, Nantes France
The role of T cells in the rejection of vascularized xenografts has
been little 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, alterations in molecular interactions could
impair the T cell response. Because the 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 recipients treated
with a combination of cobra venom factor and cyclosporin A (CsA), to
analyze T cell infiltration and, for the first time, Vß TCR usage, at
the complementarity-determining region 3 level, in accommodated and
rejected xenografts, compared with allografts. After withdrawal of CsA
(on day 40), the analysis of Vß family expression and corresponding
complementarity-determining region 3 lengths in rejected xenografts
revealed a Gaussian pattern, in contrast to a much more restricted
pattern in rejected allografts (p = 0.002),
suggesting that, after withdrawal of CsA, all the underrepresented T
cell clones are rapidly expanded in xenografts. These results correlate
with the rapid kinetics of rejection (4 ± 1 days), the high
number of T cells, the rapid expression of markers of activation (IL-2
receptor 
-chain and class II receptor), and the strong deposit of
IgG Abs in rejected xenografts. Taken together, these results suggest
that the intensity and diversity of the T cell response to xenografts
could be stronger than the response to allografts in
vivo.
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