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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cooke, K. R. Articles by Ferrara, J. L.M. Search for Related Content PubMed PubMed Citation Articles by Cooke, K. R. Articles by Ferrara, J. L.M. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 7 (October 1), 1998: pp. 2571-2580 Host Reactive Donor T Cells Are Associated With Lung Injury After Experimental Allogeneic Bone Marrow Transplantation Kenneth R. Cooke, Werner Krenger, Geoff Hill, Thomas R. Martin, Lester Kobzik, Joanne Brewer, Raymond Simmons, James M. Crawford, Marcel R.M. van den Brink, and James L.M. Ferrara From the Department of Pediatric Oncology, Dana-Farber Cancer Institute; the Department of Pathology, Brigham and Women's Hospital; the Division of Pediatric Pulmonology, Children's Hospital, Boston, MA; and the Department of Pathology, Yale University School of Medicine, New Haven, CT. Noninfectious lung injury is common after allogeneic bone marrow transplantation (BMT), but its association with acute graft-versus-host disease (GVHD) is unclear. Using a murine BMT system where donor and host differ by multiple minor histocompatibility (H) antigens, we investigated the nature of lung injury and its relationship both to systemic GVHD and host-reactive donor T cells. Lethally irradiated CBA hosts received syngeneic BMT or allogeneic (B10.BR) T-cell-depleted (TCD) bone marrow (BM) with and without the addition of T cells. Six weeks after BMT, significant pulmonary histopathology was observed in animals receiving allogeneic BMT compared with syngeneic controls. Lung damage was greater in mice that received allogeneic T cells and developed GVHD, but it was also detectable after TCD BMT when signs of clinical and histologic acute GVHD were absent. In each setting, lung injury was associated with significant alterations in pulmonary function. Mature, donor (V6+ and V3+) T cells were significantly increased in the broncho-alveolar lavage (BAL) fluid of all allogeneic BMT recipients compared with syngeneic controls, and these cells proliferated and produced interferon- (IFN-) to host antigens in vitro. These in vitro responses correlated with increased IFN- and tumor necrosis factor- (TNF-) in the BAL fluid. We conclude that alloreactive donor lymphocytes are associated with lung injury in this allogeneic BMT model. The expansion of these cells in the BAL fluid and their ability to respond to host antigens even when systemic tolerance has been established (ie, the absence of clinical GVHD) suggest that the lung may serve as a sanctuary site for these host reactive donor T cells. These findings may have important implications with regard to the evaluation and treatment of pulmonary dysfunction after allogeneic BMT even when clinical GVHD is absent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Levis, R. Loi, K. J. Butnor, P. Vacek, C. Steele, B. T. Mossman, and D. J. Weiss Decreased Asbestos-Induced Lung Inflammation and Fibrosis after Radiation and Bone Marrow Transplant Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 16 - 25. [Abstract] [Full Text] [PDF] S. W. Choi, G. C. Hildebrandt, K. M. Olkiewicz, D. A. Hanauer, M. N. Chaudhary, I. A. Silva, C. E. Rogers, D. T. Deurloo, J. M. Fisher, C. 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