Effect of CD8+ T Cell Depletion in Acute Lung Allograft Rejection in Mice

Abstract

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, acute allograft rejection of lungs is independent of CD4+ T cell allorecongnition pathways. We investigated the role of CD8+ T cells predominantly found in rejected lungs. Methods: Lung allografts from C57BL/6 mice were transplanted orthotopically into fully MHC-mismatched BALB/c (H-2d) recipients. Recipients received anti-CD4mAb or anti-CD8 mAb (100μg i.p., d-2, d-1, d0). Depletion was confirmed by FACS analysis of blood and spleen. 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 by flow cytometry at different time-points in recipient groups. Results: In contrast to syngeneic grafts, which revealed normal appearance at day 7, allografts displayed severe acute rejection with extensive perivascular and interstitial infiltrates of mononuclear cells. CD4+ depleted recipients rejected their grafts at the same time as the untreated recipients. In the untreated recipients, the percentage of infiltration of CD8+ T cells was significantly superior to that of CD4+ T cells. However, CD8+ depleted recipients displayed no enhancement of graft survival compared to wild-type control recipients. Conclusion: This is the first report indicating that both CD4+ and CD8+T cells can independently reject lung allografts in mice.