Amount of co-transplanted donor-derived leukocytes determines in-vivo microchimerism and mixed lymphocyte culture changes post-liver transplantation

Objective: To evaluate the impact of passenger leukocytes in liver grafts on the rate of microchimerism induction after liver transplantation and to evaluate immunological changes thereafter based on serial donor-specific MLCs in these patients. Methods: 26 orthotopic liver transplant recipients were prospectively evaluated for immunological changes based on the co-transplantation 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: HLA-PCR 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 mm(2) liver tissue (SD +/- 23.2 cells/mm(2), range 121 to 217 cells per mm(2) tissue). Other-wise patients without chimerism showed a mean of 90.4 passenger leukocytes per mm(2) tis- sue (SD +/- 14.5 cells/mm(2), range: 52 to 99 cells/mm(2)). 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% to 88%) in the 15 patients with stable microchimerism. Otherwise in the 11 patients without microchimerism dsmMLC resuits stayed at continuously higher levels with a mean of 106% (SD +/- 13.4, range 92% to 134%). Conclusions: 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.