| Popis: |
To evaluate cardiac allografts from recipients that had achieved peripheral tolerance after transient CD4+ T cell depletion, we analyzed cellular infiltrate, cytokine expression, and vascular thickening. Long-surviving cardiac allografts from tolerant recipients were compared with acutely rejecting allografts and isografts.In CBA mice treated with anti-CD4 (GK1.5, 0.5 mg intraperitoneally on days 1-28), BALB/c cardiac allografts survived100 days. These recipients were tested for tolerance at70 days, by challenge with donor and third-party (C57BL/6) skin grafts. BALB/c skin grafts survived30 days, although C57BL/6 skin was rejected in12 days, reflecting alloantigen-specific peripheral tolerance. When vascular thickening in graft arteries was assessed and computerized measurements performed, heart allografts from tolerant recipients showed significantly increased percentage of luminal occlusion compared with isografts (47% compared with 1.2%). Semiquantitative reverse transcriptase-polymerase chain reaction was used to assess normalized intragraft mRNA transcripts for cytokines and T cell markers, with immunoperoxidase staining of frozen sections to confirmed the presence of protein. Compared with rejecting grafts, well-preserved hearts from tolerant mice had lower levels of macrophage and T cell infiltration and decreased transcription of interferon-gamma, interleukin (IL)-2, IL-10, and inducible nitric oxide synthase. IL-4 expression was similar in both groups.The degree of tolerance achieved allowed specific acceptance of donor skin grafts, preserved primary graft function, and reduced inflammatory activation. Tolerance did not, however, completely prevent macrophage and T cell infiltration of the graft or the development of vascular lesions typical of chronic rejection. |
