The discovery of the presence of previously unsuspected microchimerism in successful longterm liver and kidney transplant recipients prompted us to postulate that these cells are essential for graft acceptance and the induction of donor-specific hyporeactivity. [1][2][3] This observation provided the basis for the initiation of a new therapeutic strategy which involved infusion of donor bone marrow (BM) cells under conventional immunosuppressive treatment with tacrolimus and prednisolone. 4 The initial outcome of sequential in vitro immunologic evaluations performed to determine the development of donor-specific hyporeactivity in the first 15 BM-augmented and 16 contemporaneous controls has been described previously. 5,6 We report here the immune profile of 102 BM-augmented and 57 control patients who were at least 6 months posttransplantation.
MATERIALS AND METHODS
Case MaterialSince December 1992, 138 study patients have received simultaneous BM + whole organ transplants. Ninety-two recipients of whole organs for whom permission could not be obtained for BM procurement from cadaveric donors were monitored as controls. Sequential immune monitoring was possible in 102 study (liver n = 31, kidneys n = 27, kidney + pancreas n = 19, kidney + islets n = 6, heart n = 10, lung n = 8) and 57 control (liver n = 23, kidney n = 10, kidney + pancreas n = 7, kidney + islets n = 2, heart n = 9, and lung n = 6) patients who were at least 180 days posttransplantation and for whom donor cells were available. Immunosuppression was similar in both groups and consisted of tacrolimus and prednisolone. 4 All patients were analyzed for donor chimerism by FACS and/or polymerase chain reaction (PCR) using HLA-specific markers. 4
In Vitro Immune ResponsivenessPre-and serially posttransplant (5, 4, and 3 times in 1st, 2nd and 3rd year respectively) monitoring of recipient's immune status was carried out by evaluating the proliferative responses of the peripheral blood mononuclear cells (PBMC)
RESULTS AND DISCUSSIONIn transplant recipients who were augmented with BM, with the exception of those receiving hearts, progressive donor-specific immunomodulation was achieved in 50%. On the contrary, only 18 of 57 (32%) of the control patients exhibited hyporeactivity or intermediate responses to the donor (DSHI). It is noteworthy that the temporal relationship of monitoring was comparable in both study and control recipients (Tables 1 and 2).
Liver Transplant RecipientsBM-augmented liver transplant recipients developed stable DSHI within the first year posttransplantation and 13 of 15 patients retested remained DSHI at the 2-year follow-up (range 200 to 600 days). In contrast, in those who received only a liver, only three of seven recipients who exhibited DSHI previously maintained persistent immunomodulation (data not shown). Two of the BM-augmented liver recipients exhibited low proliferative responses to mitogens, donors, and third-party alloantigens and were considered suppressed. The majority of study (87%) and control (100%) recipients...
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