| First Author | Sun K | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 2033-42 |
| PubMed ID | 22778394 | Mgi Jnum | J:189757 |
| Mgi Id | MGI:5446963 | Doi | 10.4049/jimmunol.1102853 |
| Citation | Sun K, et al. (2012) IFN-gamma receptor-deficient donor T cells mediate protection from graft-versus-host disease and preserve graft-versus-tumor responses after allogeneic bone marrow transplantation. J Immunol 189(4):2033-42 |
| abstractText | Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN-gamma. However, the consequence of Th17-associated lung GVHD in the presence of IFN-gamma has not been well characterized. In the current study, T cells from IFN-gamma receptor knockout (IFN-gammaR(-/-)) mice, capable of producing IFN-gamma but unable to signal in response to IFN-gamma, have been used to elucidate further the role of IFN-gamma in GVHD. We found the transfer of donor T cells from either IFN-gammaR(-/-) or IFN-gamma knockout (IFN-gamma(-/-)) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL-4-producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-gammaR(-/-) T cells. Notably, despite the presence of these cells, these mice did not show the severe immune-mediated histopathological lung injury observed in mice receiving donor IFN-gamma(-/-) T cells. Increases in lung GVHD did occur in mice with donor IFN-gammaR(-/-) T cells when treated in vivo with anti-IFN-gamma demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-gammaR(-/-) T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-gammaR(-/-) T cells versus wild-type donor T cells displayed similar graft-versus-tumor (GVT) effects. These results demonstrate the critical role of IFN-gamma on host tissues and cell effector functions in GVHD/GVT. |
