DIFFERENTIAL USAGE OF THE T-CELL RECEPTOR REPERTOIRE FOR ALLORECOGNITION OF HEART, LIVER, AND KIDNEY GRAFTS

We have previously demonstrated that the immune response to cardiac allografts in the ACI-to-LEW rat strain combination involves a limited use of the TCR V beta gene repertoire. In the present study we analyzed the expression of V beta genes by T cells infiltrating kidney and liver allografts to test whether a limited use of the T cell receptor (TCR) repertoire is a common denominator for immune responses to allografts. Graft-infiltrating lymphocytes (GIL) were isolated from allografts on different days after transplantation and analyzed for the expression of V beta genes using a semiquantitative polymerase chain reaction (PCR) without manipulations in tissue culture. We detected a limited expression of the V beta gene repertoire in fresh GIL harvested from both kidney and liver allografts early in graft rejection. The level of TCR repertoire usage, however, was influenced by the type of graft. The rejection of heart and kidney allografts was associated with more limited use of the V beta gene repertoire when compared with that seen for the rejection of liver allografts. The limited use of the V beta gene repertoire was only apparent when analyzed early in graft rejection; as the rejection reaction progressed T cells using a more diverse V beta repertoire infiltrated the graft. The limited use of TGR repertoire of the early T cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T cell populations for elimination at the time of organ transplantation.