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Institut National de la Santé et de la Recherche Médicale Unité 437 "Immunointervention dans les allo-et xeno-transplantations" and Institut de Transplantation et de Recherche en Transplantation, Nantes, France
Donor-specific allograft tolerance can be induced in the adult rat by pregraft donor-specific blood transfusion (DST). This tolerance appeared to be mediated by regulatory cells and to the production of the suppressive cytokine TGF-ß1. A potential immunoregulatory CD8+ clone bearing a Vß18-Dß1-Jß2.7 TCR gene rearrangement was previously identified in DST-treated recipients. To assess the functional role of this T cell clone in the induction of tolerance by DST, we have vaccinated DST-treated recipients with a plasmid construct encoding for the Vß18-Dß1-Jß2.7 TCR ß-chain. DST-induced allograft tolerance was abolished by anti-TCR Vß18-Dß1-Jß2.7 DNA vaccination in six of seven recipients, whereas vaccination with the vector alone, or with the construct encoding a TCR Vß13 ß-chain, had no effect. However, the transcript number of the Vß18-Dß1-Jß2.7 chain was unchanged in allografts from vaccinated DST-treated rats, suggesting that this clone was not depleted by vaccination, but rather was altered in its function. Moreover, TCR Vß18-Dß1-Jß2.7 DNA vaccination restored the anti-donor alloantibody production, partially restore the capacity of spleen cells from tolerized recipients to proliferate in vitro against donor cells, and decreased the inhibitory effect of TGF-ß1, seen in DST-treated recipients, in spleen cells from vaccinated DST-treated ones. This study strongly suggests that this CD8+ TCR Vß18-Dß1-Jß2.7 T cell clone has an effective immunoregulatory function in allograft tolerance induced by DST.
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