The in vitro immune response of uremic and transplanted patients was studied by determining lymphocyte surface and functional markers. Because of lymphopenia, the absolute number of T and B cells are diminished in uremia and transplantation. The uremic state had a profound effect of T cell mitogenic response, while the relative number (%) of T cells was not reduced. B cell responses and relative numbers were significantly diminished. The early posttransplant period was associated with a significant reduction in both T and B cell response and relative numbers. All indexes returned toward normal late in the posttransplant course with reduction of immunosuppression and cessation of the uremic state. Horse anti-human lymphocyte globulin treatment caused a significant reduction in T cells and an increase in B cells. Prednisone therapy did not appear to influence the relative number of the lymphocyte subpopulation but did reduce the mitogenic responses. Changes in surface or functional markers did not prove useful in predicting rejection episodes in transplanted patients.

The metabolism of azathioprine (AZA) was studied by monitoring the concentrations of red blood cell (RBC) 6-thioguanine nucleotides (6-TGN) and of 6-methylmercaptopurine metabolites (6-mMP) in 27 renal transplantation recipients and in 10 patient subjects with glomerulonephritis (GN). Concentrations of 6-TGNs and 6-mMP metabolites were measured using high-performance liquid chromatography (HPLC). Six patients from the group of renal transplantation recipients were also administered allopurinol. Median values of RBC 6-TGN and of 6-mMP metabolites concentrations in 21 renal transplantation recipients (without allopurinol) were 122 pmol/8x10(8) RBCs (range, <60-298) and 280 pmol/8x10(8) RBC (range, <150-1330), respectively; there was no correlation between concentrations of 6-TGN and of 6-mMP metabolites. The group of 21 renal transplantation recipients received different AZA doses (100 or 50 mg/d) related to clinical symptoms of AZA intolerance. The median values of 6-TGN concentrations in these subgroups were 131 and 122 pmol/8x10(8) RBCs and were not significantly different. Median values of 6-TGN concentrations in patients given allopurinol were significantly higher, despite AZA dose reduction, compared with the group without allopurinol and were equal to 363 and 122 pmol/8x10(8) RBC, p < 0.004, respectively. No significant differences were found between the concentrations of 6-mMP metabolites in either group. In the group of renal transplantation recipients, a significant correlation between white blood cell (WBC) count and 6-TGN concentration was established (r(s) = -0.59, p < 0.005). In the group of GN patients, the median values of 6-TGN and of 6-mMP metabolites concentrations were 108 pmol/8x10(8) RBCs (range, 0-297) and 420 pmol/8x10(8) RBC (range, 0-1440), respectively. There were no significant correlations between either the WBC count and 6-TGN concentrations or between 6-TGN concentrations and 6-mMP metabolites. We expect the results of our study to provide indications for better individualization of AZA therapy.

Abstract. To decrease immunogenicity of the rat kidney, grafts were perfused with an anti-MHC class li monoclonal antibody (mAb ). How effectively this procedure blocked dass li-positive cells, which were mainly dendritic in appearance, was checked by immunostaining renal sections after perfusion and comparing them with in vitro stained sections. Optimum conditions were applied for graft pretreatment before transplantation. This procedure prolonged graft survival, though not satisfactorily from the biological point ofview (9.6 ± 0.8 versus 7.7 ± 0.5 days in the control group; P < 0.02). The dendritic cells were not killed but blocked. Several hours after transplantation, the mAb dissociated from these dass li-positive cells. It was also shown that donor cells migrate into the recipient's spieen early after transplantation. The number of these cells was smaller when the transplanted organ was perfused with the mAb. Further studies are suggested to deplete the graft of donor dendritic cells more adequately. They should also combine graft perfusion with antidass II mAb and recipient immunosuppression at reduced doses.Keywords: Class II antigen blockade, rat, renal transplantation -Monoclonal antibody, dass II antigen blockadeRenal transplantation, rat, class II antigen blockadeThe immunogenicity of the graft and the immunological reactivity of the recipient are the main factors that determine allogeneic graft rejection. Immunogenicity depends on the presence of minor and major histocompatibility complex (MHC) class I and II gene products on the cell surface. It has been shown that class II antigen expression is not stable, and various protocols may change the extent to which these antigens are expressed [1,2,16,19,22,24,25). It has also been demonstrated in studies on the heart and pancreas [3,21] that rat strains may be divided into Offprint requests to: M.Krzymanski, Department of Nephrology, Institute of Internat Medicine, Academy of Medicine, Al. Przybyszewskiego 49, Poznaii 60-355, Poland two groups. One has a high density of interstitial dendritic cells (DC) that express class II antigens and the other a low density. For successful transplantationindifferent rat strain combinations, it may be advantageaus to know the dass II MHC antigen expression and to take it into account.To decrease the immunogenicity of the graft, various procedures have been used [4,9,13,14,17,18,23]. Evidence is accumulating to support the hypothesis that graft immunogenicity may be altered by pretreatment with anti-class II monoclonal antibodies. However, evidence of the effectiveness of perfusion procedures, as presented in the literature, is quite fragmentary.In the present study, MHC dass II antigen expression was investigated in rat renal grafts to analyze the effectiveness of the perfusion procedure in pretreating the graft and to define the optimum conditions for blocking dass II antigens expressed on DC. The efficacy of the method was assessed morphologically by the immunoperoxidase technique on renal tissue sections. Kidneys p...

To decrease immunogenicity of the rat kidney, grafts were perfused with an anti-MHC class II monoclonal antibody (mAb). How effectively this procedure blocked class II-positive cells, which were mainly dendritic in appearance, was checked by immunostaining renal sections after perfusion and comparing them with in vitro stained sections. Optimum conditions were applied for graft pretreatment before transplantation. This procedure prolonged graft survival, though not satisfactorily from the biological point of view (9.6 +/- 0.8 versus 7.7 +/- 0.5 days in the control group; P less than 0.02). The dendritic cells were not killed but blocked. Several hours after transplantation, the mAb dissociated from these class II-positive cells. It was also shown that donor cells migrate into the recipient's spleen early after transplantation. The number of these cells was smaller when the transplanted organ was perfused with the mAb. Further studies are suggested to deplete the graft of donor dendritic cells more adequately. They should also combine graft perfusion with anti-class II mAb and recipient immunosuppression at reduced doses.

No abstract