Anzahl der „Passenger“ Leukozyten im Lebertransplantat (LTx) bestimmt Entstehung eines in-vivo Mikrochimärismus und Ausmaß von MLC-Reduzierung nach LTx

Abstract

Background and Methods: Between January 1997 and May 1999 26 orthotopic liver transplant recipients were prospectively evaluated for immunological changes based on the cotransplantation of donor-derived leukocytes. Intraoperatively harvested liver biopsies and peripheral blood lymphocytes of liver transplant recipients were sampled at various time points. Donor spleen cells were obtained during organ procurement. Results: HLAPCR analysis demonstrated a stable pattern of microchimerism in 15 out of 26 patients. Microchimerism was detectable by PCR up to a mean of 7 weeks after transplantation, when chimerism in the peripheral blood became negative. Passenger donor leukocytes were present in all biopsies obtained during backtable preparation of the liver graft. For the 15 patients presenting microchimerism the rate of passenger leukocytes in the liver graft biopsies showed a mean of 155.8 leukocytes per mm2 liver tissue (SD ± 23.2 cells/mm2, range 121 to 217 cells per mm2 tissue). Otherwise, patients without chimerism showed a mean of 90.4 passenger leukocytes per mm2 tissue (SD ± 14.5 cells/mm2, range 52 – 99 cells/mm2). Lymphocyte proliferation, determined by donor-specific „multiple“ single-way mixed-lymphocyte cultures (dsmMLC) was reduced to a mean of 62.2% of preoperative values (SD ±14.5%, range 33% – 88%) in the 15 patients with stable microchimerism. Otherwise, in the 11 patients without microchimerism dsmMLC results stayed at continuously higher levels with a mean of 106% (SD ±13.4, range 92% – 134%). When third party lymphocytes were used as stimulators in the same dsmMLC setup of chimeric liver graft recipients, no reduction was present, suggesting that the decreased immune reactivity of chimeric recipient lymphocytes seems to be a donor-specific effect. Conclusion: The results from these studies of microchimerism and lymphocyte reactivity after liver transplantation suggest that the co-transplantation of donor leukocytes plays an important and active role in the modulation of the host immune system.