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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2249-2257. Prepublished online as a Blood First Edition Paper on November 16, 2004; DOI 10.1182/blood-2004-08-3320. This Article Full Text (PDF) All Versions of this Article: 2004-08-3320v1 105/6/2249    most recent Alert me when this article is cited Alert me if a correction is posted 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hildebrandt, G. C Articles by Cooke, K. R Search for Related Content PubMed PubMed Citation Articles by Hildebrandt, G. C Articles by Cooke, K. R Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2004 Accepted November 1, 2004 Donor T cell-production of RANTES significantly contributes to the development of Idiopathic Pneumonia Syndrome after allogeneic stem cell transplantation Gerhard C Hildebrandt, Krystyna M Olkiewicz, Sung Choi, Leigh A Corrion, Shawn G Clouthier, Chen Liu, Jonathan S Serody, and Kenneth R Cooke* Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA; Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA Department of Pathology, University of Florida School of Medicine, Gainesville, FL, USA Division of Hematology/Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA * Corresponding author; email: krcooke{at}med.umich.edu. Idiopathic pneumonia syndrome (IPS) is a major cause of mortality following allogeneic stem cell transplantation (allo-SCT). Clinical and experimental data support a role for conditioning-induced inflammation and allo-reactive T cell responses in IPS pathophysiology, but the mechanisms by which donor leukocytes are ultimately recruited to the lung are not fully understood. RANTES is a chemokine ligand that is upregulated during inflammation and promotes the recruitment of T cells and macrophages to sites of tissue damage. Using a lethally irradiated murine SCT model (B6B6D2F1), we evaluated the role of donor leukocyte derived RANTES in the development of IPS. Pulmonary mRNA and protein levels of RANTES were significantly elevated in allo-SCT recipients compared to syngeneic controls and were associated with enhanced mRNA expression of CCR5 and CCR1 and with inflammatory cell infiltration into the lung. Allo-SCT with RANTES-/- donor cells significantly decreased IPS and improved survival. Combinations of allogeneic wild-type or RANTES-/- bone marrow with wild-type or RANTES-/- T cells, demonstrated that the expression of RANTES by donor T cells was critical to the development of lung injury after SCT. These data reveal that donor T cells can help regulate leukocyte recruitment to the lung after allo-SCT and provide a possible mechanism through which inflammation engendered by SCT conditioning regimens is linked to allo-specific T cell responses during the development of IPS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Cascading lung injury in allogeneic SCT Georgia B. Vogelsang Blood 2005 105: 2247-2248. [Full Text] [PDF]

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