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DOI: 10.1055/s-0035-1544474
Effect of CD4+ /CD8+ T-cell Depletion in Acute Lung Allograft Rejection in Mice
Background: Despite contemporary immunosuppression protocols, acute allograft rejection remains a major obstacle to successful lung transplantation. We and others previously showed that, unlike in other solid organs, depletion of CD4+ and CD 8+ T-cells can lead to lung allograft rejection each independently of the other. Here we investigated the effects of combined CD4 and CD8 T cell depletion in acute allograft rejection.
Methods: Lung allografts from C57BL/6 were transplanted orthotopically into fully MHC-mismatched BALB/c (H-2d) recipients. Recipients received anti-CD 4mAb and anti-CD8 mAb (100µg i.p., d-2, d-1, d0). Depletion was confirmed by FACS analysis of blood, spleen and allograft. In the syngeneic group, C57BL/6 grafts were transplanted into C57BL/6 recipients. Rejection was confirmed by direct visualization after thoracotomy. On day 7 post transplantation, grafts were examined by immunohistology and flow cytometry. Titers of immunoglobulin were measured at different time-points in recipient groups.
Results: In contrast to syngeneic grafts, which revealed normal appearance at day 7, allografts with CD4+/CD8+ depletion displayed severe acute rejection with extensive perivascular and interstitial infiltrates of NK-cells and macrophages. Interestingly, acute graft rejection occurred in a similar time course as in untreated or single depleted animals, although both CD4+ and CD8+ immune responses were inhibited.
Conclusion: This is the first report that demonstrates in a model of CD4/CD8+ T cell depletion that NK-cells and macrophages seem to be sufficient to cause lung allograft rejection.