Indications of immunological tolerance in kidney transplantation.
As a complication to immunosuppressive treatment in allotransplantation, malignant diseases such as post-transplant lymphoproliferative disorder (PTLD) may occur. The patient in the present case is a 21-year-old man transplanted at the age of 11 with a kidney from his mother and at the age of 15 with a kidney from his father. During the immunosuppressive treatment the patient developed PTLD resulting in the withdrawal of the immunosuppressive drugs. At the time of writing, the immunosuppressive drugs have been withdrawn for more than 3 years. We report the findings of a state of donor-specific tolerance occurring after transplantation. Post-transplant cells from the patient show a non-reactive response in mixed lymphocyte cultures (MLCs) to cells from both the mother and the father. We demonstrate a reduction in the mRNA expression of the Thl cytokines IL-2 and IFN-gamma in the very same MLCs. The expression 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 MLCs with patient cells against cells from a paternal HLA-A, B and DR-matched individual, suggesting the influence of other allorecognition factors than HLA-A, B and DR. Detection in vitro of a lowered expression of Th1 cytokine mRNA supports the notion of these mRNAs as indicators of post-transplant tolerance. Further studies will reveal whether the cytokine mRNA measurements on short time stimulated lymphocytes can be used more generally as a monitoring parameter of tolerance in kidney transplantation.
Department of Clinical Immunology, Aarhus University Hospital, Denmark.
L L
LL
Christensen
N
N
Grunnet
N
N
Rüdiger
B
B
Møller
S A
SA
Birkeland
D000328:Adult; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology; D008297:Male
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D007371:Interferon-gamma