TOLERANCE INDUCTION BY INTRATHYMIC INOCULATION PREVENTS CHRONIC RENAL-ALLOGRAFT REJECTION

Background. These experiments investigated the ability of the donor-sp ecific unresponsiveness created by the intrathymic inoculation of dono r alloantigen to effectively prevent chronic rejection in an establish ed rat model of chronic renal allograft rejection. Methods. Three stud y groups were examined: (1) Allograft controls-F-344 rats received a L ewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls-F-344 rats received an F-344 renal isograft and low- dose CsA; (3) experimental group-F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis b one marrow. Twenty-one days after bone marrow transplant, these animal s received a Lewis renal allograft. Results. Allograft controls demons trated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analys is revealed increased CD4(+) T cells infiltrating the cortex of the al lograft controls. Cytokine interferon-gamma and interleukin-2 transcri pts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcrip tase-polymerase chain reaction. Analysis of tolerant grafts by flow mi crofluorimetry and genomic DNA amplification could not detect chimeris m to a level of <0.1%. Conclusion. IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.