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• W2024108085 abstract "P895 Aims: Hypoparathyroidism is an endocrine dysfunction that is associated with reduced blood calcium levels due to insufficient levels of parathyroid hormone (PTH). The best known treatment is the transplantation of parathyroid glands. In order to prevent graft rejection without general immunosuppression it is necessary to get more knowledge about the immune response to allogeneic parathyroid glands. Methods: Male hypocalcaemic Lewis rats (LEW, RT1l) received parathyroid glands under the kidney capsule from Wistar-Furth (WF, RT1avl) or LEW rats (syngeneic control). Calcium serum levels were detected repeatedly after transplantation. Levels higher than 2.0 mmol/l proved function of the transplant, levels lower than 2.0 mmol/l indicated transplant rejection (Microsurgery, 2003). At various time points grafts were explanted and expression of inducible nitric oxide synthase (iNOS) were determined by RT-PCR. Grafts were also examined for infiltration of inflammatory immunocompetent host cells by immunohistochemistry. Some of the LEW rats were immunized prior to transplantation with P1, a synthetic peptide derived from the MHC class I molecules of WF. P1 induces a strong activation of alloreactive LEW T cells (Human Immunol, 2002). Some glands were depleted of passenger leukocytes prior to transplantation by in vitro cultivation. Results: LEW rats transplanted syngeneically returned to normal serum calcium levels. In the allogeneic transplanted animals serum calcium levels stayed normal until rejection on day 15±2. During this time period the allografts were continuously infiltrated by recipient’s leukocytes mainly T cells and macrophages. Activated MHC-class II positive, ED1-positive macrophages were observed on day 2 after transplantation within the allografts, on day 3 T cells were additionally detected. Few activated (CD25+) T cells appeared on day 4 and stayed within the infiltrate during the whole examination period. In activated macrophages the expression of iNOS was shown. LEW rats immunized with peptide P1 showed accelerated rejection at day 10±1. Depletion of passenger leukocytes had no effect on the onset of rejection. Conclusions: Direct allorecognition apparently is not important for the rejection of parathyroid allografts, since the depletion of passenger leukocytes did not prolong graft function. Alloreactive T cells activated by the indirect pathway of allorecognition after immunization with peptide P1 led to accelerated rejection. This indicates that T cells are involved in allograft destruction. In non-immunized animals only a low amount of activated T cells within the graft was detected. In contrast, the strong presence of activated MHC-class II positive macrophages in allografts of non-immunized LEW rats indicates their involvement in graft rejection. These macrophages produce the cytotoxic effector NO. Therefore therapeutic strategies should include the inhibition of macrophage infiltration and their allogeneic activation." @default.
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• W2024108085 date "2004-07-01" @default.
• W2024108085 modified "2023-10-17" @default.
• W2024108085 title "THE ROLE OF ALLOANTIGEN-INDUCED ACTIVATION OF T CELLS AND MACROPHAGES IN PARATHYROID ALLOGRAFT REJECTION" @default.
• W2024108085 doi "https://doi.org/10.1097/00007890-200407271-01391" @default.
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