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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.


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PLENARY PAPERS

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

From the Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI; the Department of Hematology and Oncology, University of Regensburg, Germany; the Department of Pathology, University of Florida School of Medicine, Gainesville, FL; and the Division of Hematology/Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.

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 alloreactive 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 up-regulated during inflammation and promotes the recruitment of T cells and macrophages to sites of tissue damage. Using a lethally irradiated murine SCT model (B6 -> B6D2F1), 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.


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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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