title: Analysis of post-transplant immune status in recipients of liver/bone marrow allografts.
abstract: The aims of this study were to assess the effect of donor bone marrow infusion on the reactivity of recipient peripheral blood lymphocytes (PBL) to mitogen and to donor and third-party cells after primary liver allotransplantation and to identify any correlation between altered immunoreactivity and HLA mismatches, occurrence of rejection, and immunosuppression. The immunoreactivity of recipient PBL toward frozen donor splenocytes was evaluated in mixed lymphocyte culture (MLC) (n = 29) and cell-mediated lympholysis (CML) (n = 27) assays in time intervals ranging from 0.7 to 27 months after transplant. Overall, the mean anti-donor MLC stimulation index (SI) fell from 25.6 +/- 5.2 preoperatively to 4.8 +/- 1.7 after transplantation (p < 0.002), with 14 out of 29 (48.3%) patients developing donor-specific MLC hyporeactivity. HLA class II mismatches were significantly associated with recipient post-transplant immune profile (p < 0.05): MLC donor specific hyporesponsiveness was observed in 70%, versus 37% of patients who shared a class II antigen, versus those that did not. Of the control group, 61.1% developed donor-specific nonreactivity versus 27.2% in the donor bone marrow cells (DBMC) group (p = 0.02). Donor-specific CML hyporeactivity was observed after transplantation, independent of DBMC infusion, with mean percentage values of pre- and post-transplant donor-specific lysis of 22.4% +/- 4.1% versus 3.1% +/- 1.6%, p = 0.0004, respectively. Our results suggest that DBMC infusion favors development of nonspecific MLC hyporesponsiveness to donor and third-party alloantigen, with maintenance of reactivity to mitogen and no additional effect on T-cell cytotoxicity.
authors.affiliation: Department of Surgery, University of Miami, School of Medicine, Florida 33136, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Chatzipetrou
authors.forename: J M
authors.initials: JM
authors.lastname: Mathew
authors.forename: N S
authors.initials: NS
authors.lastname: Kenyon
authors.forename: V
authors.initials: V
authors.lastname: Esquenazi
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: A G
authors.initials: AG
authors.lastname: Tzakis
mesh_terms: D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D006084:Graft Rejection; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens