Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year.

Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. Four multicolor, non-overlapping flow cytometry protocols were used to assess the immunophenotypes. Mixed cell cultures with donor or third party cells were used to measure cell proliferation and interferon gamma production. Despite a significant overlap, simultaneous liver-kidney transplant recipients had a lower overall frequency of circulating CD8, activated CD4 and effector memory T cells, compared to solitary kidney transplant recipients. Simultaneous liver-kidney transplant recipient T cells had a significantly lower proliferative response to the donor cells compared to solitary kidney recipients (11.9 vs. 42.9%), although their response to third party cells was unaltered. The frequency of interferon gamma producing alloreactive T cells in simultaneous liver-kidney transplant recipients was significantly lower than that of solitary kidney transplant recipients. Flow cytometric analysis of the mixed cultures demonstrated that both alloreactive CD4 and CD8 compartments of the simultaneous liver-kidney transplant recipient circulating blood cells were smaller. Thus, the phenotypic and functional characteristics of the circulating blood cells of the simultaneous liver-kidney transplant recipients resembled those of solitary liver transplant recipients, and appear to be associated with donor-specific hypo-alloresponsiveness.