INDICATIONS OF IMMUNOLOGICAL-TOLERANCE IN KIDNEY-TRANSPLANTATION

As a complication to immunosuppressive treatment in allotransplantatio n, malignant diseases such as post-transplant lymphoproliferative diso rder (PTLD) may occur. The patient in the present case is a 21-yearold man transplanted at the age of 11 with a kidney from his mother and a t the age of 15 with a kidney from his father. During the immunosuppre ssive treatment the patient developed PTLD resulting in the withdrawal of the immunosuppressive drugs. At the time of writing, the immunosup pressive drugs have been withdrawn for more than 3 years. We report th e findings of a state of donor-specific tolerance occurring after tran splantation. Posttransplant cells from the patient show a non-reactive response in mixed lymphocyte cultures (MLCs) to cells from both the m other and the father. We demonstrate a reduction in the mRNA expressio n of the Th1 cytokines IL-2 and IFN-gamma in the very same MLCs. The e xpression of Th1 cytokine mRNA was measured semi-quantitatively using competitive reverse transcription-polymerase chain reaction (RT-PCR). The reduction in the Th1 cytokine mRNA expression is not seen in the M LCs with patient cells against cells from a paternal HLA-A, B and DR-m atched individual, suggesting the influence of other allorecognition f actors than HLA-A, B and DR. Detection in vitro of a lowered expressio n of Th1 cytokine mRNA supports the notion of these mRNAs as indicator s of post-transplant tolerance. Further studies will reveal whether th e cytokine mRNA measurements on short time stimulated lymphocytes can be used more generally as a monitoring parameter of tolerance in kidne y transplantation.