DONOR-SPECIFIC BLOOD TRANSFUSION-INDUCED TOLERANCE IN ADULT-RATS WITHA DOMINANT TCR-V-BETA REARRANGEMENT IN HEART ALLOGRAFTS

Following allotransplantation, determinants encoded within the donor M HC are recognized by recipient T lymphocytes through their Ag receptor , In this study, we investigated the TCR V beta chain diversity of T c ells infiltrating rejected and tolerated heart allografts in a model o f donor-specific blood transfusion-induced tolerance in MHC-mismatched congeneic rats. The PCR-based method that we used allows the diversit y of V beta chains at the complementarity-determining region 3 level t o be analyzed quantitatively, Our results show that the V beta reperto ire usage in graft-infiltrating T cells was characteristic and differe nt in tolerated compared with rejected grafts, and differed in both ca ses from the normal distribution of the V beta repertoire. An expansio n of lymphocytes showing a conserved V beta 18-D beta 1-J beta 2.7 gen e rearrangement was found, from the first day after grafting onward, i n graft-infiltrating cells from all tolerant animals. This clone accou nted for as much as 5% of the whole V beta repertoire in tolerated hea rts, as evidenced by RNase protection assay, In contrast, we demonstra ted that, of lymphocytes infiltrating rejected grafts, those with a V beta 18 chain were diverse, and that even though by day 5 the conserve d V beta 18-D beta 1-J beta 2.7 rearrangement was detectable, lymphocy tes harboring this rearrangement represented less than 0.6% of the who le TCR-alpha beta(+) T cell repertoire, Kinetics analysis revealed tha t the expansion of lymphocytes bearing this conserved rearrangement wa s elicited specifically by donor blood transfusion, Indeed, V beta 18- D beta 1-J beta 2.7 transcripts were detected in PBL from transfused a nimals as early as 7 days after donor-specific blood transfusion, Fina lly, we provided evidence that this T cell clone belongs to the CD8(+) subset, The putative role in inducing and maintaining the allograft t olerance of the CD8(+) T tell clone harboring this public V beta 18-D beta 1-J beta 2.7 rearrangement is discussed.